title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Inhibition of transforming growth factor β signaling promotes epiblast formation in mouse embryos. | Early lineage segregation in preimplantation embryos and maintenance of pluripotency in embryonic stem cells (ESCs) are both regulated by specific signaling pathways. Small molecules have been shown to modulate these signaling pathways. We examined the influence of several small molecules and growth factors on second-lineage segregation of the inner cell mass toward hypoblast and epiblast lineage during mouse embryonic preimplantation development. We found that the second-lineage segregation is influenced by activation or inhibition of the transforming growth factor (TGF)β pathway. Inhibition of the TGFβ pathway from the two-cell, four-cell, and morula stages onward up to the blastocyst stage significantly increased the epiblast cell proliferation. The epiblast formed in the embryos in which TGFβ signaling was inhibited was fully functional as demonstrated by the potential of these epiblast cells to give rise to pluripotent ESCs. Conversely, activating the TGFβ pathway reduced epiblast formation. Inhibition of the glycogen synthase kinase (GSK)3 pathway and activation of bone morphogenetic protein 4 signaling reduced the formation of both epiblast and hypoblast cells. Activation of the protein kinase A pathway and of the Janus kinase/signal transducer and activator of transcription 3 pathway did not influence the second-lineage segregation in mouse embryos. The simultaneous inhibition of three pathways--TGFβ, GSK3β, and the fibroblast growth factor (FGF)/extracellular signal-regulated kinases (Erk)--significantly enhanced the proliferation of epiblast cells than that caused by inhibition of either TGFβ pathway alone or by combined inhibition of the GSK3β and FGF/Erk pathways only. | 25,245,024 | [
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Inhibition of protein phosphatase 2A with a small molecule LB100 radiosensitizes nasopharyngeal carcinoma xenografts by inducing mitotic catastrophe and blocking DNA damage repair. | Nasopharyngeal carcinoma (NPC), while uncommon worldwide, is a major health problem in China. Although local radiation and surgery provide good control of NPC, better treatments that permit reductions in radiation dosing are needed. Inhibition of protein phosphatase 2A (PP2A), a ubiquitous multifunctional enzyme with critical roles in cell cycle regulation and DNA-damage response, reportedly sensitizes cancer cells to radiation and chemotherapy. We studied PP2A inhibition with LB100, a small molecule currently in a Phase I clinical trial, on radiosensitization of two human nasopharyngeal cell lines: CNE1, which is reportedly radioresistant, and CNE2. In both cell lines, LB100 exposure increased intracellular p-Plk1, TCTP, and Cdk1 and decreased p53, changes associated with cell cycle arrest, mitotic catastrophe and radio-inhibition of cell proliferation. Mice bearing subcutaneous xenografts of either cell line were administered 1.5 mg/kg LB100 daily for three days and a single dose of 20 Gy radiation (day 3), which produced marked and prolonged tumor mass regression (dose enhancement factors of 2.98 and 2.27 for CNE1 and CNE2 xenografts, respectively). Treatment with either LB100 or radiation alone only transiently inhibited xenograft growth. Our results support further exploration of PP2A inhibition as part of radiotherapy regimens for NPC and potentially other solid tumors. | 25,245,035 | [
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Effectiveness and toxicity of high-dose cyclophosphamide in obese versus non-obese patients receiving allogeneic hematopoietic stem cell transplant. | To determine if there is a difference in toxicity and effectiveness between obese and non-obese patients who receive high-dose cyclophosphamide (Cy) prior to allogeneic hematopoietic stem cell transplant (allo-HCT). Patients were included in this study if they were at least 18 years of age and received high-dose Cy in combination with total body irradiation (CyTBI) or busulfan (BuCy) prior to allo-HCT between 1 January 2008 and 29 February 2012. The primary endpoint was the difference in overall toxicity between obese and non-obese patients. Secondary objectives examined differences in effectiveness between groups assessed by relapse at day +100, relapse at 1 year, death at 1 year, chimerisms at days +30, +60, and +90, and incidence of acute graft versus host disease (aGVHD). Sixty-one patients met the inclusion criteria, 28 obese and 33 non-obese. Overall toxicity was greater in obese patients compared to non-obese patients (82% vs. 52%, OR 4.3 [95% CI 1.3-14.1]; p = 0.01), which was driven by a greater incidence of renal dysfunction (79% vs. 48%, OR 3.9 [95% CI 1.3-12.1]; p = 0.02). There were no differences in rates of grade 3 or 4 toxicity, hepatic dysfunction, or any measure of effectiveness between groups. Obese patients receiving high-dose Cy and allo-HCT are at increased risk for toxicity, although there appears to be no difference in the rate of relapse or survival between obese and non-obese patients. | 25,245,037 | [
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Heterogeneity in venous disease practice patterns amongst primary healthcare practitioners. | This study aimed to describe the practice patterns of primary healthcare practitioners who diagnose and manage venous disease to determine differences in clinical evaluation of disease, recognition of venous ulcers, and referral patterns. A survey was distributed at the August 2011 Primary Care Medical Conference (Pri-Med) in Baltimore, Maryland. Pri-med is a medical education company that caters to the continued professional development needs of a variety of physicians. A total of 305 surveys were completed. Of the respondents, 91% were physicians and 9% were advanced level practitioners. In all, 93% prescribed compression stockings as first-line treatment. Heterogeneous referral patterns were reported with 81% referring to vascular surgery, 25% to a vein clinic, 10% to interventional radiology, and 3% to interventional cardiology. Up to 35% responded that they met resistance (did not have their referral accepted) when attempting referral to a vascular surgery colleague. There was substantial variation when asked about the treatment of deep vein thrombosis with 88% starting anticoagulation therapy, 54% prescribing compression stockings, 40% doing a thrombophilia workup, and 25% referring for lytic therapy. Diagnosis and management aptitude of venous disease is highly variable. Further grassroots education is required to improve diagnosis and treatment in patients with chronic venous disease. | 25,245,047 | [
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A moving overlay shrinks the attentional blink. | This report describes a study examining the effects of overlaying a veil of spots on the letters in a central rapid serial visual presentation stream. Observers identified two target letters (T1 and T2, respectively) embedded in a stream of distractor letters printed in a different color. In Experiment 1, the attentional blink (AB) diminished when a different overlay veiled each letter, such that the spots appeared to move as the letters changed. Experiment 2 concerned whether the performance enhancement occurred because the overlay hampered processing of the lag 1 distractor, thus weakening the distractor's interference with T1. Experiment 3 focused on how changing the overlay at or around T1 affected the AB. The attention disengagement hypothesis was proposed to explain the common theme in the results-that performance was only enhanced when different overlays were applied to the T1 and lag 1 frames. The claim is that the AB reflects a failure of prompt attentional disengagement from T1, which, in turn, delays reengagement when T2 appears shortly thereafter. When T1's disappearance is accompanied by an overlay change, the perceptual system gets an additional cue signaling that the visual scene has changed, thereby inducing attentional disengagement. Apart from facilitating prompt reengagement at the next target, earlier disengagement also improves target recovery by excluding features of the trailing item, likely to be a distractor, from working memory. | 25,245,077 | [
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Gene therapy for chronic granulomatous disease: current status and future perspectives. | Several Phase I/II clinical trials aiming at the correction of X-linked CGD by gene transfer into hematopoietic stem cells (HSCs) have demonstrated the therapeutic potential of gene modified autologous HSCs for the treatment of CGD. Resolution of therapy-resistant bacterial and fungal infections in liver, lung and spinal canal of CGD patients were clearly documented in all trials. However, clinical benefits were not sustained over time due to the failure of gene transduced cells to engraft long-term. Moreover, severe adverse effects were observed in some of the treated patients due to insertional mutagenesis leading to the activation of growth promoting genes and to myeloid malignancy. These setbacks fostered the development of novel safety and efficacy improved vectors that have already entered or are about to enter the clinics. Meanwhile, ongoing research is constantly refining the CGD disease phenotype, including the definition of factors that may explain the unique engraftment phenotype observed in CGD gene therapy trials. This review provides a condensed overview on the current knowledge of the molecular pathomechanisms and clinical manifestations of CGD and summarizes the lessons learned from clinical gene therapy trials, the preclinical progress in vector design and the future perspectives for the gene therapy of CGD. | 25,245,086 | [
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Layered double hydroxides as an effective additive in polymer gelled electrolyte based dye-sensitized solar cells. | Layered double hydroxides (LDH), a class of anionic clay materials, were developed as an effective additive for polymer gelled electrolytes for use in dye-sensitized solar cells (DSSC). Carbonate and chloride intercalated Zn-Al LDHs, ZnAl-CO3 LDH, and ZnAl-Cl LDH were prepared with coprecipitation methods. The addition of the two LDHs significantly improved, in terms of power conversion efficiency (PCE), over the plain poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) gelled electrolyte and competed favorably with the liquid electrolyte based DSSCs, 8.13% for the liquid electrolyte, 7.48% for the plain PVDF-HFP gelled electrolyte, 8.11% for the ZnAl-CO3 LDH/PVDF-HFP gelled electrolyte, and 8.00% for the ZnAl-Cl LDH/PVDF-HFP gelled electrolyte based DSSCs. The good performance in PCEs achieved by the LDH-loaded DSSCs came mainly from the significant boost in open circuit voltages (Voc), from 0.74 V for both the liquid electrolyte and PVDF-HFP gelled electrolyte based DSSCs to 0.79 V for both the ZnAl-CO3 LDH/PVDF-HFP and ZnAl-Cl LDH/PVDF-HFP gelled electrolyte based DSSCs. The boost in Voc was contributed mainly by the positive shift in redox potential of the redox couple, I(-)/I3(-), as revealed from cyclic voltammetry analyses. As for the long-term stability, PCE retention rates of 96 and 99% after 504 h were achieved by the ZnAl-CO3 LDH/PVDF-HFP and ZnAl-Cl LDH/PVDF-HFP gelled electrolyte based DSSCs, respectively, appreciably better than 92% achieved by the liquid electrolyte based one after 480 h. | 25,245,099 | [
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Risk of leukaemia and residential exposure to air pollution in an industrial area in Northern Italy: a case-control study. | Leukaemia risk in adult populations exposed to environmental air pollution is poorly investigated. We have carried out a population-based case-control study in an area that included a fossil fuel power plant, a coke oven and two big chemical industries. Information on residential history and several risk factors for leukaemia was obtained from 164 cases, diagnosed between 2002 and 2005, and 279 controls. A higher risk for subjects residing in polluted areas was observed, but statistical significance was not reached (adjusted OR = 1.11 and 1.56 for subjects living in moderately and in heavily polluted zones, respectively, p = 0.190). Results suggest a possible aetiological role of residential air pollution from industrial sites on the risk of developing leukaemia in adult populations. However, the proportion of eligible subjects excluded from the study and the lack of any measure of air pollution prevent definitive conclusions from being drawn. | 25,245,102 | [
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FoxO3 is a negative regulator of primary CD8+ T-cell expansion but not of memory formation. | The generation of CD8(+) T cells by vaccination represents an important goal for protective immunity to infectious pathogens. It is thus of utmost importance to understand the mechanisms involved in the generation of optimal CD8(+) T-cell responses. The forkhead box O (FoxO) family of transcription factors has a crucial role in cellular responses to environmental change. Among them, FoxO3 is critically involved in the regulation of cellular proliferation, apoptosis, metabolism and stress resistance to withdrawal of nutrients or cytokine growth factors. Since the role of FoxO3 has been poorly studied in the immune system, here we have evaluated its involvement in the CD8(+) T-cell response. We observe that CD8(+) T cells deficient for FoxO3 undergo a significantly greater primary expansion than their wild-type (WT) counterparts in response to both infectious (vaccinia virus) or non-infectious (non-replicating cellular vaccine) immunogens, resulting in a larger cohort of cells following contraction. These survivors, however, do not undergo a greater secondary response than WT. Taken together, our data show that FoxO3 is a negative regulator of the CD8(+) T-cell response, specifically during the primary expansion. | 25,245,112 | [
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Outcomes after subtotal parathyroidectomy for primary hyperparathyroidism due to hyperplasia: significance of whole vs. partial gland remnant. | Primary hyperparathyroidism (PHPT) due to multigland hyperplasia is managed by subtotal parathyroidectomy (sPTX), with a partial gland left in situ. However, smaller, hyperplastic glands may be encountered intraoperatively, and it is unclear if leaving an intact gland is an equivalent alternative. This study evaluates the rates of permanent hypoparathyroidism and cure of PHPT patients with four-gland hyperplasia that were left with either a whole gland remnant (WGR) or a partial gland remnant (PGR) after sPTX. We reviewed the outcomes of PHPT patients with hyperplasia who underwent sPTX at an academic institution. Surgeon intraoperative judgment determined remnant size (a WGR vs. a PGR). Between 2002 and 2013, 172 patients underwent sPTX for PHPT. There were 108 patients (62.8%) who had a WGR. Another 64 patients (37.2%) had a PGR. Mean age was 60 ± 14 years. There were 82.6% female patients. Cases with positive family history for PHPT were more likely to have a PGR (12.5 vs. 3.7%; p = 0.03). Patients had similar preoperative and postoperative laboratories. Individuals with a PGR tended to have larger glands encountered by surgeons intraoperatively (525 ± 1,308 vs. 280 ± 341 mg; p = 0.02). One patient with a WGR developed permanent hypocalcemia. Overall, the cure rate was 97.1%. A mean of 29 ± 28.7 months follow-up revealed a recurrence rate of 5.2%. Disease persistence and recurrence rates were similar in patients. PHPT due to hyperplasia is managed by sPTX, leaving WGR without increased rates of disease persistence/recurrence. Patients without family history for hyperparathyroidism and those with smaller glands may be the best candidates for this approach. | 25,245,126 | [
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Perceived control and intrinsic vs. extrinsic motivation for oral self-care: a full factorial experimental test of theory-based persuasive messages. | Correlational evidence suggests that perceived control (PC) and intrinsic motivation (IM), key constructs in social cognitive and self-determination theories, may interact to reinforce behavior change. This proof-of-principle study examines the independent and synergistic effects of interventions to increase PC and IM upon dental flossing frequency. University students (n = 185) were randomized in a 2 × 2 full factorial design to receive two computer-based interventions: one to either increase or decrease PC and another to increase either IM or extrinsic motivation. These constructs were measured immediately post-intervention; flossing behavior was measured 1 week later. The interventions to increase PC and PC/IM had main and interaction effects on flossing, respectively. The PC/IM interaction effect was mediated by increases in PC and IM. Combining interventions to increase PC and IM seems to be a promising avenue of research, which has implications for both theory and intervention development. | 25,245,138 | [
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FAAH-mediated modulation of TLR3-induced neuroinflammation in the rat hippocampus. | The present study examined the effect of enhancing fatty acid amide hydrolase (FAAH) substrate levels in vivo on Toll-like receptor (TLR)3-induced neuroinflammation. Systemic and central (i.c.v.) administration of the FAAH inhibitor URB597 increased hippocampal levels of the N-acylethanolamines palmitoylethanolamide and oleoylethanolamide, but not anandamide. Systemic URB597 increased IFNα, IFNγ and IL-6 expression following TLR3 activation and attenuated TLR3-induced IL-1β and TNFα expression. In comparison, central URB597 administration attenuated the TLR3-induced increase in TNFα and IFNγ expression (and associated downstream genes IP-10 and SOCS1), while concurrently increasing IL-10 expression. These data support an important role for FAAH-mediated regulation of TLR3-induced neuroinflammatory responses. | 25,245,162 | [
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Qualitative evaluation of the relevance and acceptability of a web-based HIV prevention game for rural adolescents. | African Americans in the rural Southern United States continue to experience disproportionate increases in new HIV/AIDS infections. Electronic gaming interventions hold promise but the use of HIV prevention games is limited. The purpose of this study was to assess the acceptability and relevance of a web-based HIV prevention game for African American rural adolescents. Findings from focus groups conducted with 42 participants suggested that the game was educational and somewhat entertaining but lacking in real-life scenarios and player-control. Findings are congruent with self-efficacy literature and constructivist approaches to learning. Findings have implications for gaming intervention development and further research. | 25,245,160 | [
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Migraine is associated with altered processing of sensory stimuli. | Migraine is associated with derangements in perception of multiple sensory modalities including vision, hearing, smell, and somatosensation. Compared to people without migraine, migraineurs have lower discomfort thresholds in response to special sensory stimuli as well as to mechanical and thermal noxious stimuli. Likewise, the environmental triggers of migraine attacks, such as odors and flashing lights, highlight basal abnormalities in sensory processing and integration. These alterations in sensory processing and perception in migraineurs have been investigated via physiological studies and functional brain imaging studies. Investigations have demonstrated that migraineurs during and between migraine attacks have atypical stimulus-induced activations of brainstem, subcortical, and cortical regions that participate in sensory processing. A lack of normal habituation to repetitive stimuli during the interictal state and a tendency towards development of sensitization likely contribute to migraine-related alterations in sensory processing. | 25,245,197 | [
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Carbapenem resistance in a human clinical isolate identified to be closely related to Acinetobacter indicus. | Here we report a case of carbapenem resistance in a human clinical isolate that was found to be closely related to the newly described environmental species Acinetobacter indicus. This strain harboured the blaOXA-23 carbapenemase gene located on a conjugative plasmid. Partial sequencing of 16S rDNA and rpoB genes, together with matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) analysis, showed that this strain was distantly related to the Acinetobacter baumannii-calcoaceticus complex and was closely related to A. indicus. | 25,245,212 | [
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IVUS-based FSI models for human coronary plaque progression study: components, correlation and predictive analysis. | Atherosclerotic plaque progression is believed to be associated with mechanical stress conditions. Patient follow-up in vivo intravascular ultrasound coronary plaque data were acquired to construct fluid-structure interaction (FSI) models with cyclic bending to obtain flow wall shear stress (WSS), plaque wall stress (PWS) and strain (PWSn) data and investigate correlations between plaque progression measured by wall thickness increase (WTI), cap thickness increase (CTI), lipid depth increase (LDI) and risk factors including wall thickness (WT), WSS, PWS, and PWSn. Quarter average values (n = 178-1016) of morphological and mechanical factors from all slices were obtained for analysis. A predictive method was introduced to assess prediction accuracy of risk factors and identify the optimal predictor(s) for plaque progression. A combination of WT and PWS was identified as the best predictor for plaque progression measured by WTI. Plaque WT had best overall correlation with WTI (r = -0.7363, p < 1E-10), cap thickness (r = 0.4541, p < 1E-10), CTI (r = -0.4217, p < 1E-8), LD (r = 0.4160, p < 1E-10), and LDI (r = -0.4491, p < 1E-10), followed by PWS (with WTI: (r = -0.3208, p < 1E-10); cap thickness: (r = 0.4541, p < 1E-10); CTI: (r = -0.1719, p = 0.0190); LD: (r = -0.2206, p < 1E-10); LDI: r = 0.1775, p < 0.0001). WSS had mixed correlation results. | 25,245,219 | [
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HPLC-DAD analysis, antioxidant potential and anti-urease activity of Asparagus gracilis collected from District Islamabad. | Asparagus gracilis subspecie of Asparagus capitatus Baker, is described as food and medicine for various ailments. In this study we investigated, its phenolic constituents, in vitro antioxidant potential against various free radicals and anti-urease potential. Asparagus gracilis aerial parts collected from District Islamabad, Pakistan were extracted with crude methanol which was further fractionated into n-hexane, ethyl acetate, n-butanol and aqueous fraction. Total phenolic and flavonoid contents were estimated for extract and all the derived fractions. Diverse in vitro antioxidants assays such as DPPH, H2O2, •OH, ABTS, β-carotene bleaching assay, superoxide radical, lipid peroxidation, reducing power, and total antioxidant capacity were studied to assess scavenging potential. Antiurease activity of methanol extract and its derived fractions was also investigated. HPLC-DAD analysis of crude methanol extract was performed by using different phenolic standards. Ethyl acetate fraction expressed maximum content of flavonoids (240.6 ± 6.1 mg RE/g dry sample), phenolics (615 ± 13 mg GAE/g dry sample) and best antioxidant potential among different fractions of crude methanol extract. Hydrogen peroxide assay and hydroxyl, supeoxide, nitric oxide free radicals antioxidant assays as well as beta carotene assay showed significant correlation with flavonoid content while hydrogen peroxide, ABTS and lipid peroxidation assay displayed significant correlation with phenolic content. HPLC analysis showed the presence of important phenolics i.e. catechin (4.04 ± 0.02 μg/mg sample), caffeic acid (0.89 ± 0.003 μg/mg sample), rutin (24.58 ± 0.1 μg/mg sample), myricetin (1.13 ± 0.07 μg/mg sample) and quercetin (14.91 ± 0.09 μg/mg sample). Ethyl acetate fraction expressed lowest IC50 in antiurease activity. Correlation analysis of antiurease activity expressed significant correlation with flavonoids (P < 0.004) and phenolics (P < 0.02) proposing multipotent activity of fractions. These results revealed the presence of some bioactive compound in the ethyl acetate fraction having both antioxidant as well as antiurease potential. | 25,245,231 | [
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Sphingosine-1-phosphate and ceramide are associated with health and atresia of bovine ovarian antral follicles. | The follicle destiny towards ovulation or atresia is multi-factorial in nature and involves outcries, paracrine and endocrine factors that promote cell proliferation and survival (development) or unchain apoptosis as part of the atresia process. In several types of cells, sphingosine-1-phospate (S1P) promotes cellular proliferation and survival, whereas ceramide (CER) triggers cell death, and the S1P/CER ratio may determine the fate of the cell. The aim of present study was to quantify S1P and CER concentrations and their ratio in bovine antral follicles of 8 to 17 mm classified as healthy and atretic antral follicles. Follicles were dissected from cow ovaries collected from a local abattoir. The theca cell layer, the granulosa cells and follicular fluid were separated, and 17β-estradiol (E2) and progesterone (P4) concentrations were measured in the follicular fluid by radioimmunoassay. Based on the E2/P4 ratio, the follicles were classified as healthy (2.2±0.3) or atretic (0.2±0.3). In both follicular compartments (granulosa and theca cell layer), sphingolipids were extracted and S1P and CER concentrations were quantified by HPLC (XTerra RP18; 5 µm, 3.0×150 mm column). Results showed that in both follicular compartments, S1P concentrations were higher in healthy antral follicles than in atretic antral follicles (P<0.05). The concentration of CER in the granulosa cells was higher in atretic antral follicles than in healthy antral follicles, but no differences were observed in the theca cell layer. The S1P/CER ratio in both follicular compartments was also higher in healthy antral follicles. Interestingly, in these follicles, there was a 45-fold greater concentration of S1P than CER in the granulosa cells (P<0.05), whereas in the theca cell layer, S1P had only a 14-fold greater concentration than CER when compared with atretic antral follicles. These results suggest that S1P plays a role in follicle health, increasing cellular proliferation and survival. In contrast, reduction of S1P and the S1P/CER in the antral follicle could trigger cellular death and atresia. | 25,245,232 | [
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Elastin-derived peptides stimulate trophoblast migration and invasion: a positive feedback loop to enhance spiral artery remodelling. | Elastin breakdown in the walls of uterine spiral arteries during early pregnancy facilitates their transformation into dilated, high-flow, low-resistance channels. Elastin-derived peptides (EDP) can influence cell migration, invasion and protease activity, and so we hypothesized that EDP released during elastolysis promote extravillous trophoblast (EVT) invasion and further elastin breakdown. Treatment of the trophoblast cell line SGHPL4 with the elastin-derived matrikine VGVAPG (1 μg/ml) significantly increased total elastase activity, promoted migration in a wound healing assay and increased invasion through Matrigel-coated transwells compared with vehicle control (0.1% DMSO) or the scrambled sequence VVGPGA. Furthermore, treatment of first-trimester placental villous explants with this EDP significantly increased both the area of trophoblast outgrowth and distance of migration away from the villous tips. Primary first-trimester cytotrophoblast exposed to VGVAPG (1 μg/ml) for 30 min showed increased phosphorylation of endothelial nitric oxide synthase and activation of the mitogen activated protein kinase pathway, events also associated with tumour cell migration and invasion. These in vitro observations suggest liberation of bioactive EDP during induction of elastolysis in the uterine spiral arteries may orchestrate a positive feedback loop that promotes EVT invasion and further elastin breakdown, contributing to the process of vascular remodelling. | 25,245,255 | [
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The noisy encoding of disparity model of the McGurk effect. | In the McGurk effect, incongruent auditory and visual syllables are perceived as a third, completely different syllable. This striking illusion has become a popular assay of multisensory integration for individuals and clinical populations. However, there is enormous variability in how often the illusion is evoked by different stimuli and how often the illusion is perceived by different individuals. Most studies of the McGurk effect have used only one stimulus, making it impossible to separate stimulus and individual differences. We created a probabilistic model to separately estimate stimulus and individual differences in behavioral data from 165 individuals viewing up to 14 different McGurk stimuli. The noisy encoding of disparity (NED) model characterizes stimuli by their audiovisual disparity and characterizes individuals by how noisily they encode the stimulus disparity and by their disparity threshold for perceiving the illusion. The model accurately described perception of the McGurk effect in our sample, suggesting that differences between individuals are stable across stimulus differences. The most important benefit of the NED model is that it provides a method to compare multisensory integration across individuals and groups without the confound of stimulus differences. An added benefit is the ability to predict frequency of the McGurk effect for stimuli never before seen by an individual. | 25,245,268 | [
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Amphipathic tail-anchoring peptide is a promising therapeutic agent for prostate cancer treatment. | Amphipathic tail-anchoring peptide (ATAP) derived from the human anti-apoptotic protein Bfl-1 is a potent inducer of apoptosis by targeting mitochondria permeability transition. By linking ATAP to an internalizing RGD peptide (iRGD), selective targeting for ATAP to tumor cell was achieved. Confocal fluorescence microscopy showed that ATAP-iRGD could penetrate into cancer cells and distribute along the mitochondria network. ATAP-iRGD triggered mitochondria-dependent cell death through release of cytochrome c. In an effort to promote ATAP-iRGD physiochemical properties to approach clinic application, amino acid substitution and chemical modification were made with ATAP-iRGD to improve its bioactivity. One of these modified peptides, ATAP-iRGD-M8, was with improved stability and aqueous solubility without compromising in vitro cytotoxicity in cultured cancer cells. In vivo xenograft studies with multiple prostate cancer cell lines showed that intravenous administration of ATAP-iRGD-M8 suppressed tumor growth. Toxicological studies revealed that repetitive intravenous administration of ATAP-iRGD-M8 did not produce significant toxicity in the SV129 mice. Our data suggest that ATAP-iRGD-M8 is a promising agent with high selectivity and limited systemic toxicity for prostate cancer treatment. | 25,245,280 | [
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Shedding of epithin/PRSS14 is induced by TGF-β and mediated by tumor necrosis factor-α converting enzyme. | Epithin/PRSS14, a type II transmembrane serine protease, plays critical roles in cancer metastasis. Previously, we have reported that epithin/PRSS14 undergoes ectodomain shedding in response to phorbol myristate acetate (PMA) stimulation. In this study, we show that transforming growth factor-β (TGF-β) induces rapid epithin/PRSS14 shedding through receptor mediated pathway in 427.1.86 thymoma cells. Tumor necrosis factor-α converting enzyme (TACE) is responsible for this shedding. Amino acid sequence encompassing the putative shedding cleavage site of epithin/PRSS14 exhibit strong homology to the cleavage site of l-selectin, a known TACE substrate. TACE inhibitor, TAPI-0 and TACE siRNA greatly reduced TGF-β-induced epithin/PRSS14 shedding. TGF-β treatment induces translocation of intracellular pool of TACE to the membrane where epithin/PRSS14 resides. These findings suggest that TGF-β induces epithin/PRSS14 shedding by mediating translocation of epithin/PRSS14 sheddase, TACE, to the membrane. | 25,245,289 | [
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Understanding and controlling type I collagen adsorption and assembly at interfaces, and application to cell engineering. | Collagen is a large anisotropic and self-assembling extracellular matrix protein. Understanding and controlling its adsorption and assembly at interfaces is expected to increase our general knowledge of protein adsorption as well as to open the way to the development of biointerfaces of interest for biomaterials science and tissue engineering. The work related to type I collagen adsorption performed in our laboratory over the past twenty years is reviewed. Substrate chemical nature and adsorption conditions (collagen concentration, adsorption duration) were shown to affect collagen adsorbed amount and supramolecular organization. Collagen assemblies were formed starting from the interface, and assembly was favored by hydrophobic substrates and high adsorbed amount. Substrates were designed to better control collagen adsorption and assembly. The spatial control of adsorption was ensured by chemically heterogeneous substrates, which also affected collagen assembly when domains with a dimension smaller than the length of the collagen molecule (i.e. 300nm) were prepared. Mixed polymer brushes were used to achieve a temporal control of adsorption: adsorption and desorption were reversibly triggered by changes of pH and ionic strength. Layer-by-layer assembly of collagen in a nanoporous template was used to elaborate collagen-based nanotubes, which were further deposited on ITO glass substrates by electrophoretic deposition. Finally, the evaluation of cell behavior on the created biointerfaces showed that the control of collagen organization can be successfully used to alter cell behavior. | 25,245,299 | [
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Effects of weight loss on foot structure and function in obese adults: a pilot randomized controlled trial. | To investigate the effects of weight reduction on foot structure, gait, and dynamic plantar loading in obese adults. In a 3-month randomized-controlled trial, participants were randomized to receive either a weight loss intervention based on portion-controlled meals or a delayed-treatment control. 41 adults (32 F, 9 M) with a mean ± SD age of 56.2 ± 4.7 years and a BMI of 35.9 ± 4.2 kg/m(2). Arch Height Index (AHI), Malleolar Valgus Index (MVI), spatial and temporal gait parameters, plantar peak pressure (PP) and weight were measured at baseline, 3, and 6 months. The intervention group experienced significantly greater weight loss than did the control group (5.9 ± 4.0 kg versus 1.9 ± 3.2 kg, p = 0.001) after 3 months. There were no differences between the groups in anatomical foot structure or gait. However, the treatment group showed a significantly reduced PP than the control group beneath the lateral arch and the metatarsals 4 (all p values < .05) at 3 months. The change in PP correlated significantly with the change in weight at the metatarsal 2 (r = 0.57, p = 0.0219), metatarsal 3 (r = 0.56, p = 0.0064) and the medial arch (r = 0.26, p < 0.0001) at 6 months. This was the first RCT designed to assess the effects of weight loss on foot structure, gait, and plantar loading in obese adults. Even a modest weight loss significantly reduced the dynamic plantar loading in obese adults. However, weight loss appeared to have no effects on foot structure and gait. | 25,245,307 | [
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[The elderly in radiotherapy: myths and prospects]. | In this single-center retrospective case-control study, 62 patients were divided into two age groups (80 years and older versus less than 65 years) treated with external beam radiation during the same period. The main objective was to investigate differences in care between these two populations. Two parameters appear statistically different between the two groups: the indication of patient weight (reported for 39% of elderly patients versus 71% of younger patients, p=0.039) and hypofractioned radiotherapy (61% and 23% of patients respectively, p=0.002). No significant difference was found for the purpose of this radiotherapy (curative or palliative), the terms of this treatment, place the patient's life and monitoring. The oncogeriatrics was born of a partnership between medical oncologists and geriatricians, it would be now useful to further develop collaboration with radiation oncologists. | 25,245,312 | [
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Bone mineral density in women with polycystic ovary syndrome. | PCOS is a complex disorder and various features of this disorder may have great importance for bone metabolism. The aim of the study was to determine the relationship between existing hormonal disorders, and bone mineral density (BMD) in young women with PCOS. 69 reproductive-aged PCOS women and 30 age-matched healthy controls were enrolled to the study women. In each individual we assessed the body mass index (BMI). We evaluated the serum concentrations of: gonadotropins, prolactin (PRL), estradiol (E2), dehydroepiandrosterone sulfate (DHEAS), testosterone (T), thyroid stimulating hormone (TSH), free thyroxine (fT4). We used the Homeostatic Model Assessment-Insulin Resistance Index (HOMA-IR) to diagnose insulin resistance. Bone mineral density in the lumbar spine was measured by dual-energy X-ray absorptiometry (DXA). The PCOS women had lower BMD values as compared to the controls (1.057 ± 0.1260 vs. 1.210 ± 0.1805 g/cm(2), p < 0.0002). In the analysis of PCOS patients according to BMI, only in the subgroup of the normal weight PCOS we find significantly lower BMD in comparison to controls (p = 0.0049). In patients with PCOS, BMD was positively correlated with insulin concentration and HOMA-IR. In the controls Z-score values were positively correlated with insulin concentration and HOMA-IR. The deleterious effect of estrogen deficiency on bones in PCOS is not balanced by androgen overproduction. Women with PCOS had significantly lower BMD of the lumbar spine compared to controls. Insulin seems to be one of the most important positive bone growth stimulators. | 25,245,338 | [
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Early generalized overgrowth in autism spectrum disorder: prevalence rates, gender effects, and clinical outcomes. | Although early head and body overgrowth have been well documented in autism spectrum disorder (ASD), their prevalence and significance remain unclear. It is also unclear whether overgrowth affects males and females differentially, and whether it is associated with clinical outcomes later in life. To evaluate prevalence of somatic overgrowth, gender effects, and associations with clinical outcomes, head circumference, height, and weight measurements were collected retrospectively between birth and 2 years of age in toddlers with ASD (n = 200) and typically developing (TD; n = 147) community controls. Symptom severity, verbal, and nonverbal functioning were assessed at 4 years. Abnormalities in somatic growth in infants with ASD were consistent with early generalized overgrowth (EGO). Boys but not girls with ASD were larger and exhibited an increased rate of extreme EGO compared to community controls (18.0% versus 3.4%). Presence of a larger body at birth and postnatal overgrowth were associated independently with poorer social, verbal, and nonverbal skills at 4 years. Although early growth abnormalities in ASD are less common than previously thought, their presence is predictive of lower social, verbal, and nonverbal skills at 4 years, suggesting that they may constitute a biomarker for identifying toddlers with ASD at risk for less-optimal outcomes. The results highlight that the search for mechanisms underlying atypical brain development in ASD should consider factors responsible for both neural and nonneural tissue development during prenatal and early postnatal periods, and can be informed by the finding that early overgrowth may be more readily observed in males than in females with ASD. | 25,245,350 | [
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Increased risk of autism spectrum disorders at short and long interpregnancy intervals in Finland. | Both short and long interpregnancy intervals (IPI) are believed to present possible adverse conditions for fetal development. Short IPI has recently been associated with increased risk of autism, but whether long IPI increases risk for autism spectrum disorders (ASD) has not been thoroughly investigated. We investigated the association between short and long IPI in a Finnish population-based study. This study was conducted in the Finnish Prenatal Study of Autism, which is based in a national birth cohort. Children born in Finland in 1987 to 2005 and diagnosed with ASD by 2007 were identified through the Finnish Hospital Discharge Register. A total of 2,208 non-firstborn patients with ASD and 5,163 matched controls identified from the Finnish Medical Birth Register were included in the primary analysis. The association between IPI and ASD was determined using conditional logistic regression and adjusted for potential confounders. Relative to births with an IPI of 24 to 59 months, those with the shortest IPI (<12 months) had an increased risk of ASD (odds ratio [OR] = 1.50, 95% CI = 1.28, 1.74) in confounder-adjusted models, whereas the ORs for longer IPI births (60-119 months and ≥120 months) were 1.28 (95% CI = 1.08, 1.52) and 1.44 (95% CI = 1.12, 1.85), respectively. This study provides evidence that risk of ASD is increased at long as well as short IPI. | 25,245,351 | [
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Attention-deficit/hyperactivity disorder polygenic risk scores predict attention problems in a population-based sample of children. | Clinically, attention-deficit/hyperactivity disorder (ADHD) is characterized by hyperactivity, impulsivity, and inattention and is among the most common childhood disorders. These same traits that define ADHD are variable in the general population, and the clinical diagnosis may represent the extreme end of a continuous distribution of inattentive and hyperactive behaviors. This hypothesis can be tested by assessing the predictive value of polygenic risk scores derived from a discovery sample of ADHD patients in a target sample from the general population with continuous scores of inattention and hyperactivity. In addition, the genetic overlap between ADHD and continuous ADHD scores can be tested across rater and age. The Psychiatric Genomics Consortium has performed the largest genome-wide analysis (GWA) study of ADHD so far, including 5,621 clinical patients and 13,589 controls. The effects sizes of single nucleotide polymorphisms (SNPs) estimated in this meta-analysis were used to obtain individual polygenic risk scores in an independent population-based cohort of 2,437 children from the Netherlands Twin Register. The variance explained in Attention Problems (AP) scale scores by the polygenic risk scores was estimated by linear mixed modeling. The ADHD polygenic risk scores significantly predicted both parent and teacher ratings of AP in preschool- and school-aged children. These results indicate genetic overlap between a diagnosis of ADHD and AP scale scores across raters and age groups and provides evidence for a dimensional model of ADHD. Future GWA studies on ADHD can likely benefit from the inclusion of population-based cohorts and the analysis of continuous scores. | 25,245,356 | [
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Condrosulf®: structural characterization, pharmacological activities and mechanism of action. | Condrosulf(®) is a pharmaceutical formulation containing chondroitin sulfate (CS) as an active component possessing high quality and purity and standardized properties. CS is currently applied as a SYSADOA (Symptomatic Slow Acting Drug for Osteoarthritis) agent in Europe in the treatment of osteoarthritis (OA). Furthermore, Condrosulf(®) and pharmaceutical grade CS have also been proven to possess structure-modifying effects belonging to the S/DMOAD (structure/disease modifying anti-osteoarthritis drug) class. This review summarizes current knowledge on CS/Condrosulf(®) structure and its properties, its pharmacological activity as proved by many clinical trials and metaanalysis studies and focuses attention on its mechanisms of action in the pathophysiology of osteoarthritic joint tissues. Finally, future perspectives are discussed in connection with the possibility to apply new outcome measures, such as MRI and biomarkers, which can yield important advances in the use of Condrosulf(®) as well as the development of new drugs with different structures useful in particular for the treatment of inflammatory symptoms and able to retard the progression of arthritis. | 25,245,376 | [
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Effect of long-term antihypertensive treatment on white-coat hypertension. | Limited evidence is available on the extent and frequency by which antihypertensive treatment lowers office blood pressure (BP) in white-coat hypertension (WCH). Data are even more scanty and discrepant on the corresponding effect on ambulatory BP (ABP). In the hypertensive patients of the European Lacidipine Study on Atherosclerosis (ELSA), office and ABP were measured before treatment and at 6-month (office BP) or 12-month (ABP) intervals during the 4-year administration of calcium channel blocker-based or β-blocker-based treatment. The two groups were pooled and data were analyzed separately in patients with both office and ABP elevation (n=1670; sustained hypertension) or WCH (n=251; office BP elevation only). In sustained hypertension, office and 24-hour mean systolic BP were both markedly reduced through the treatment period, the mean change being -20.0±12.5 and -10.1±11.0 mm Hg, respectively (P<0.0001 for both). In striking contrast, in WCH the office BP reduction was almost as marked as in sustained hypertension (-19.1±11.2 mm Hg; P<0.0001), whereas 24-hour systolic BP values showed no fall or a slight progressive significant increase, its mean change during treatment being 1.6±8.6 mm Hg (P=0.007). Lowering of office BP occurred at a lower treatment intensity in WCH than in sustained hypertension. Similar findings were obtained for diastolic BP. In WCH, antihypertensive treatment should not be expected to have a lowering effect on ABP, even when office BP undergoes a concomitant marked and persistent reduction. The consequence of this contrasting effect on the incidence of hypertension-related outcomes remains to be established. | 25,245,386 | [
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CYP2J2 targeting to endothelial cells attenuates adiposity and vascular dysfunction in mice fed a high-fat diet by reprogramming adipocyte phenotype. | Obesity is a global epidemic and a common risk factor for endothelial dysfunction and the subsequent development of diabetes mellitus and vascular diseases such as hypertension. Epoxyeicosatrienoic acids (EETs) are cytochrome P450 (CYP)-derived metabolites of arachidonic acid that contribute to vascular protection by stimulating vasodilation and inhibiting inflammation. Heme oxygenase-1 is a stress response protein that plays an important cytoprotective role against oxidative insult in diabetes mellitus and cardiovascular disease. We recently demonstrated interplay between EETs and heme oxygenase-1 in the attenuation of adipogenesis. We examined whether adipocyte dysfunction in mice fed a high-fat diet could be prevented by endothelial-specific targeting of the human CYP epoxygenase, CYP2J2. Tie2-CYP2J2 transgenic mice, fed a high-fat diet, had a reduction in body weight gain, blood glucose, insulin levels, and inflammatory markers. Tie2-CYP2J2 gene targeting restored HF-mediated decreases in vascular heme oxygenase-1, Cyp2C44, soluble epoxide hydrolase, phosphorylated endothelial nitric oxide synthase, phosphorylated protein kinase B, and phosphorylated adenosine monophosphate protein kinase protein expression, thus improving vascular function. These changes translated into decreased inflammation and oxidative stress within adipose tissue and decreased peroxisome proliferator-activated receptor-γ, CCAAT/enhancer binding protein alpha, mesoderm-specific transcript, and adipocyte 2 expression and increased uncoupling protein 1 and uncoupling protein 2 expression, reflecting the effect of vascular EET overproduction on adipogenesis. The current study documents a direct link between endothelial-specific EET production and adipogenesis, further implicating the EET-heme oxygenase-1 crosstalk as an important cytoprotective mechanism in the amelioration of vascular and adipocyte dysfunction resulting from diet-induced obesity. | 25,245,389 | [
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Pharyngocutaneous fistula after total laryngectomy: a single-institution experience, 2001-2012. | The purpose of this study was to determine the incidence of and risk factors for pharyngocutaneous fistula in patients undergoing total laryngectomy at a single institution. The records of 59 patients undergoing primary or salvage total laryngectomy at our institution from 2001 to 2012 were retrospectively reviewed. Data collected included patient, tumor and treatment characteristics, and surgical technique. Risk factors were analyzed for association with pharyngocutaneous fistula formation. Twenty patients (34%) developed fistulas. Preoperative tracheostomy (OR 4.1; 95% CI 1.3-13 [p=0.02]) and low postoperative hemoglobin (OR 9.1; 95% CI 1.1-78 [p=0.04]) were associated with fistula development. Regarding surgical technique, primary sutured closure of the total laryngectomy defect had the lowest fistula rate (11%). In comparison, primary stapled closure and pectoralis onlay flap over primary closure had nonsignificantly increased fistula rates (43%, OR 6.0; 95% CI 1.0-37.3 [p=0.06] and 25%, OR 2.7; 95% CI 0.4-23.9 [p=0.38], respectively). Pectoralis flap incorporated into the suture line had a significantly increased fistula rate (50%, OR 7.1; 95% CI 1.4-46 [p=0.02]). After stratification for salvage status, patient comorbidities were associated with fistula in non-salvage cases whereas disease-related characteristics were associated with fistula in salvage cases. Fistula development was associated with increased length of hospital stay (p<0.001) and increased time before oral diet initiation (p<0.001). Pharyngocutaneous fistula is a common complication of total laryngectomy. Preoperative tracheostomy, postoperative hemoglobin, and surgical technique are important in determining the risk of fistula. | 25,245,411 | [
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Soft tissue airway dimensions and craniocervical posture in subjects with different growth patterns. | To compare the dimensions of the nasopharynx and oropharynx of subjects with different growth patterns and to determine whether any correlation exists with their craniocervical posture. Cephalometric radiograph of 60 subjects (16-25 years old), taken in natural head position, were divided into three groups according to the mandibular plane angle: hypodivergent (SN/MP <26°), normodivergent (SN/MP 26°-38°), and hyperdivergent (SN/MP <38°). Correlations were calculated between nasopharyngeal area, oropharyngeal area, and craniocervical posture. Continuous variables were compared by one-way analysis of variance, and the significance of mean difference between the groups was done by the Tukey post hoc test. A value of P < .05 was considered statistically significant. Patients in the hyperdivergent group were found to have significantly smaller nasopharyngeal and oropharyngeal areas than the other groups (P < .001 and P < .05, respectively). Similarly, the oropharyngeal area in the normodivergent group was significantly smaller than that in the hypodivergent group (P < .05). However, no significant differences were found in the nasopharyngeal area between the hypodivergent and normodivergent groups and between the hyperdivergent and normodivergent groups (P > .05). Reduced pharyngeal airways were typically seen in patients with a large craniocervical angle and a large mandibular inclination. Smaller nasopharyngeal and oropharyngeal airways were seen in connection with a large craniocervical and a large mandibular inclination. We therefore suggest that the vertical skeletal pattern may be one of the factors that contribute to nasopharyngeal and oropharyngeal obstruction. | 25,245,417 | [
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Tamibarotene as maintenance therapy for acute promyelocytic leukemia: results from a randomized controlled trial. | The introduction of all-trans-retinoic acid (ATRA) has significantly improved outcomes for acute promyelocytic leukemia (APL), although a subset of patients still suffer relapse. The purpose of this study was to evaluate the role of maintenance therapy with the synthetic retinoid tamibarotene in APL. Patients with newly diagnosed APL in molecular remission at the end of consolidation therapy were randomly assigned to receive ATRA or tamibarotene, both orally, for 14 days every 3 months for up to 2 years. A total of 347 patients were enrolled. Of the 344 eligible patients, 319 (93%) achieved complete remission. After completing three courses of consolidation therapy, 269 patients underwent maintenance random assignment. The relapse-free survival (RFS) rate at 4 years was 84% for the ATRA arm and 91% for the tamibarotene arm (hazard ratio [HR], 0.54; 95% CI, 0.26 to 1.13). When the analysis was restricted to 52 high-risk patients with an initial WBC count ≥ 10.0 × 10(9)/L, the intergroup difference was statistically significant, with 4-year RFS rates of 58% for the ATRA arm and 87% for the tamibarotene arm (HR, 0.26; 95% CI, 0.07 to 0.95). For patients with non-high-risk disease, the HR was 0.82 (95% CI, 0.32 to 2.01). The test for interaction between treatment effects and these subgroups resulted in P = .075. Both treatments were generally well tolerated. In this trial, no difference was detected between ATRA and tamibarotene for maintenance therapy. In an exploratory analysis, there was a suggestion of improved efficacy of tamibarotene in high-risk patients, but this requires further study. | 25,245,439 | [
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Randomized phase III trial of retinoic acid and arsenic trioxide versus retinoic acid and chemotherapy in patients with acute promyelocytic leukemia: health-related quality-of-life outcomes. | A randomized clinical trial compared efficacy and toxicity of standard all-trans-retinoic acid (ATRA) plus chemotherapy versus ATRA plus arsenic trioxide in patients with newly diagnosed, low- or intermediate-risk acute promyelocytic leukemia (APL). Here, we report health-related quality-of-life (HRQOL) results. HRQOL was a secondary end point of this trial. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 was used to assess HRQOL at end of induction and after consolidation therapy. All analyses were based on 156 patients who received at least one dose of treatment, with groups defined according to randomly assigned treatment. Primary analysis was performed, estimating mean HRQOL score over time and differences between treatment arms using a linear mixed model. Overall, 162 patients age 18 to 70 years were enrolled. Of these, 150 and 142 patients were evaluable for HRQOL after induction therapy and third consolidation course, respectively. Overall compliance with HRQOL forms was 80.1%. The largest difference, favoring patients treated with ATRA plus arsenic trioxide, was found for fatigue severity (mean score difference, -9.3; 95% CI, -17.8 to -0.7; P = .034) at end of induction therapy. This difference was also clinically relevant. HRQOL differences between treatment arms at end of consolidation showed that for several scales, differences between treatment arms were marginal. Overall, current HRQOL findings further support the use of ATRA plus arsenic trioxide as preferred first-line treatment in patients with low- or intermediate-risk APL. | 25,245,446 | [
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Expression of leptin and its long form receptor at the porcine maternal-fetal interface: contrasting healthy and arresting conceptus attachment sites during early and mid-pregnancy. | It is well established that spontaneous conceptus loss in swine is associated with an imbalance of both angiogenic and immunological factors. Leptin (LEP), a metabolic hormone, has also been implicated in the promotion of angiogenesis. In this study, LEP and its long form receptor (OB-Rb) were evaluated during porcine pregnancy to assess their basal level of expression and their potential role in conceptus development. Expression and secretion of LEP and OB-Rb were quantified in the endometrium of non-pregnant (n = 5), and in the endometrium and chorioallantoic membrane (CAM) of pregnant sows (parity 2 to 5) at gestational days (gd) 20 (n = 8) and 50 (n = 8). Data were analyzed by a 3-way ANOVA testing the effects of conceptus health, tissue type and gestational day. Leptin and OB-Rb transcripts were significantly higher (P < 0.05) in pregnant than in non-pregnant sows. Significantly greater LEP (P < 0.001) was detected in the endometrial tissue at gd20 compared with gd50. At the protein level, the lowest LEP expression (P < 0.01) was detected in the CAM at gd50, while OB-Rb protein was significantly lower (P < 0.01) at gd50 in the CAM than in the endometrium collected from gd20 and gd50 conceptus attachment sites. Immunofluorescence staining confirmed the expression of these proteins at both gestational days and in both tissue types. Changes in the expression patterns of LEP and OB-Rb between gd20 and gd50 suggest a role for the LEP/OB-R complex at the early stages of porcine pregnancy, possibly affecting the attachment process. Further mechanistic studies are warranted to understand the specific role of leptin in porcine pregnancy. | 25,245,493 | [
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Traumatic stress, oxidative stress and post-traumatic stress disorder: neurodegeneration and the accelerated-aging hypothesis. | Post-traumatic stress disorder (PTSD) is associated with elevated risk for a variety of age-related diseases and neurodegeneration. In this paper, we review evidence relevant to the hypothesis that chronic PTSD constitutes a form of persistent life stress that potentiates oxidative stress (OXS) and accelerates cellular aging. We provide an overview of empirical studies that have examined the effects of psychological stress on OXS, discuss the stress-perpetuating characteristics of PTSD, and then identify mechanisms by which PTSD might promote OXS and accelerated aging. We review studies on OXS-related genes and the role that they may have in moderating the effects of PTSD on neural integrity and conclude with a discussion of directions for future research on antioxidant treatments and biomarkers of accelerated aging in PTSD. | 25,245,500 | [
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[RALP: comparison of the oncological and functional outcomes of the intrafascial and the interfascial approaches]. | Due to its technical ease and greater precision Robotic Assisted Laparoscopic radical Prostatectomy (RALP) allows a better preservation of the neurovascular bundles, thereby improving functional outcomes. The intrafascial dissection has been proposed to allow a more complete preservation of these bundles. However, this technique harbors a high rate of positive surgical margins, justifying another trend: the interfascial approach. To date, there are still few publications directly comparing these 2 techniques and our study is the first to offer a 2-year follow-up. Our study focused on a two-hundred patients population divided into two consecutive groups. All the patients were continent preoperatively and had a satisfactory IIEF5 score: (1) Group 1 consisted of 100 patients who underwent RALP with the intrafascial approach. They had a mean age of 60.3 years (45-70). The majority of cancers were of the low or moderate risk group of d'Amico. The mean PSA was 7.43ng/ml. Seventy-five patients had a pT2, 24 a pT3 and one patient had a pT4. (2) Group 2 included 100 patients who underwent RALP with the interfascial technique. Patients had a mean age of 61.6±5.96 years (45-72), and their cancers were mostly of the low or moderate risk groups of d'Amico. The mean PSA was 6.3ng/ml. Seventy-four patients had a pT2, 22 a pT3a, and 4 had a pT3b. All patients were evaluated after one and two years of follow-up. Rates of positive surgical margins were 45% and 19% respectively for groups 1 and 2 (P<0.0001). The rates of biochemical failure (PSA>0.2ng/ml) at 2 years were 10% and 3%, respectively for groups 1 and 2 (P=0.0447). At 2 years, 2 patients in group 1 and one patient in group 2 were using 2 or more urinary pads. Erection with or without oral medication was maintained in 65 (65%) and 31 (31%) patients respectively for groups 1 and 2 at one year. At 2 years 86 and 65 patients were having spontaneous erection, respectively in groups 1 and 2 (P=0.0006). In addition, 65 and 55 patients were also capable of sexual penetration, respectively in groups 1 and 2 (P=0.0045). The intrafascial approach exposed to a very high rate of positive surgical margins while offering only a little benefit in the erectile function preservation at 2 years compared to the interfascial variant. In our series, we did not notice any significant difference between the two techniques concerning the urinary continence. 5. | 25,245,504 | [
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Effects of using Nintendo Wii™ exergames in older adults: a review of the literature. | The purpose of this review is to summarize and synthesize the impact of using the Nintendo Wii™ exergames in older adults. A database search was conducted to identify relevant studies. The search was limited to empirical studies, with particular attention paid to the effects of Wii exergames intervention on cognition, physical function, and psychosocial outcomes in older adults. A total of 22 empirical studies met inclusion criteria and were included in this review. Positive effects included improving physical function, decreasing depression, and increasing cognition and quality of life in older adults. Improved socialization and motivation to exercise were also reported. Using Wii exergames does show promise as an intervention to improve physical function, cognition, and psychosocial outcomes in older adults. Evidence supports that Wii exergames is a safe and feasible tool to encourage older adults to engage in exercise. | 25,245,519 | [
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State of Fukushima nuclear fuel debris tracked by Cs137 in cooling water. | It is still difficult to assess the risk originating from the radioactivity inventory remaining in the damaged Fukushima nuclear reactors. Here we show that cooling water analyses provide a means to assess source terms for potential future releases. Until now already about 34% of the inventories of (137)Cs of three reactors has been released into water. We found that the release rate of (137)Cs has been constant for 2 years at about 1.8% of the inventory per year indicating ongoing dissolution of the fuel debris. Compared to laboratory studies on spent nuclear fuel behavior in water, (137)Cs release rates are on the higher end, caused by the strong radiation field and oxidant production by water radiolysis and by impacts of accessible grain boundaries. It is concluded that radionuclide analyses in cooling water allow tracking of the conditions of the damaged fuel and the associated risks. | 25,245,528 | [
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Correlation between CYP1A1 transcript, protein level, enzyme activity and DNA adduct formation in normal human mammary epithelial cell strains exposed to benzo[a]pyrene. | The polycyclic aromatic hydrocarbon (PAH) benzo(a)pyrene (BP) is thought to bind covalently to DNA, through metabolism by cytochrome P450 1A1 (CYP1A1) and CYP1B1, and other enzymes, to form r7, t8, t9-trihydroxy-c-10-(N(2)-deoxyguanosyl)-7,8,9,10-tetrahydro-benzo[a]-pyrene (BPdG). Evaluation of RNA expression data, to understand the contribution of different metabolic enzymes to BPdG formation, is typically presented as fold-change observed upon BP exposure, leaving the actual number of RNA transcripts unknown. Here, we have quantified RNA copies/ng cDNA (RNA cpn) for CYP1A1 and CYP1B1, as well as quinone oxidoreductase 1 (NQO1), which may reduce formation of BPdG adducts, using primary normal human mammary epithelial cell (NHMEC) strains, and the MCF-7 breast cancer cell line. In unexposed NHMECs, basal RNA cpn values were 58-836 for CYP1A1, 336-5587 for CYP1B1 and 5943-40112 for NQO1. In cells exposed to 4.0 µM BP for 12h, RNA cpn values were 251-13234 for CYP1A1, 4133-57078 for CYP1B1 and 4456-55887 for NQO1. There were 3.5 (mean, range 0.2-15.8) BPdG adducts/10(8) nucleotides in the NHMECs (n = 16), and 790 in the MCF-7s. In the NHMECs, BP-induced CYP1A1 RNA cpn was highly associated with BPdG (P = 0.002), but CYP1B1 and NQO1 were not. Western blots of four NHMEC strains, chosen for different levels of BPdG adducts, showed a linear correlation between BPdG and CYP1A1, but not CYP1B1 or NQO1. Ethoxyresorufin-O-deethylase (EROD) activity, which measures CYP1A1 and CYP1B1 together, correlated with BPdG, but NQO1 activity did not. Despite more numerous levels of CYP1B1 and NQO1 RNA cpn in unexposed and BP-exposed NHMECs and MCF-7cells, BPdG formation was only correlated with induction of CYP1A1 RNA cpn. The higher level of BPdG in MCF-7 cells, compared to NHMECs, may have been due to a much increased induction of CYP1A1 and EROD. Overall, BPdG correlation was observed with CYP1A1 protein and CYP1A1/1B1 enzyme activity, but not with CYP1B1 or NQO1 protein, or NQO1 enzyme activity. | 25,245,543 | [
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Job insecurity is associated with adult asthma in Germany during Europe's recent economic crisis: a prospective cohort study. | Job insecurity has been identified as a risk factor for adverse health outcomes. Perceptions of job insecurity steeply increased during Europe's recent economic downturn, which commenced in 2008. The current study assessed whether job insecurity was associated with incident asthma in Germany during this period. We used prospective data from the German Socio-Economic Panel for the period 2009-2011 (follow-up rate=77.5%, n=7031). Job insecurity was defined by respondents' ratings of the probability of losing their job within the next 2 years and asthma as self-reports of physician-diagnosed asthma. Associations between job insecurity in 2009 (continuous z-scores or categorised variables) and incident asthma by 2011 were assessed using multivariable Poisson regression. The risk of asthma increased significantly by 24% with every one SD increase of the job insecurity variable. In dichotomised analyses, a probability of job loss of ≥50% (vs <50%) was associated with a 61% excess risk of asthma. A trichotomous categorisation of job insecurity confirmed this finding. This study has shown, for the first time, that perceived job insecurity may increase the risk of new onset asthma. Further prospective studies may examine the generalisability of our findings and determine the underlying mechanisms. | 25,245,545 | [
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Biochemical measurements of beef are a good predictor of untrained consumer sensory scores across muscles. | The ability of the biochemical measurements, haem iron, intramuscular fat (IMF%), moisture content, and total, soluble and insoluble collagen contents, to predict untrained consumer sensory scores both across different muscles and within the same muscle from different carcasses were investigated. Sensory scores from 540 untrained French consumers (tenderness, flavour liking, juiciness and overall liking) were obtained for six muscles; outside (m. biceps femoris), topside (m. semimembranosus), striploin (m. longissimus thoracis), rump (m. gluteus medius), oyster blade (m. infraspinatus) and tenderloin (m. psoas major) from each of 18 French and 18 Australian cattle. The four sensory scores were weighted and combined into a single score termed MQ4, which was also analysed. All sensory scores were highly correlated with each other and with MQ4. This in part reflects the fact that MQ4 is derived from the consumer scores for tenderness, juiciness, flavour and overall liking and also reflects an interrelationship between the sensory scores themselves and in turn validates the use of the MQ4 term to reflect the scope of the consumer eating experience. When evaluated across the six different muscles, all biochemical measurements, except soluble collagen, had a significant effect on all of the sensory scores and MQ4. The average magnitude of impact of IMF%, haem iron, moisture content, total and insoluble collagen contents across the four different sensory scores are 34.9, 5.1, 7.2, 36.3 and 41.3, respectively. When evaluated within the same muscle, only IMF% and moisture content had a significant effect on overall liking (5.9 and 6.2, respectively) and flavour liking (6.1 and 6.4, respectively). These results indicate that in a commercial eating quality prediction model including muscle type, only IMF% or moisture content has the capacity to add any precision. However, all tested biochemical measurements, particularly IMF% and insoluble collagen contents, are strong predictors of eating quality when muscle type is not known. This demonstrates their potential usefulness in extrapolating the sensory data derived from these six muscles to other muscles with no sensory data, but with similar biochemical parameters, and therefore reducing the amount of future sensory testing required. | 25,245,561 | [
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Longitudinal performance of an implantable vestibular prosthesis. | Loss of vestibular function may be treatable with an implantable vestibular prosthesis that stimulates semicircular canal afferents with biphasic pulse trains. Several studies have demonstrated short-term activation of the vestibulo-ocular reflex (VOR) with electrical stimulation. Fewer long-term studies have been restricted to small numbers of animals and stimulation designed to produce adaptive changes in the electrically elicited response. This study is the first large consecutive series of implanted rhesus macaque to be studied longitudinally using brief stimuli designed to limit adaptive changes in response, so that the efficacy of electrical activation can be studied over time, across surgeries, canals and animals. The implantation of a vestibular prosthesis in animals with intact vestibular end organs produces variable responses to electrical stimulation across canals and animals, which change in threshold for electrical activation of eye movements and in elicited slow phase velocities over time. These thresholds are consistently lower, and the slow phase velocities higher, than those obtained in human subjects. The changes do not appear to be correlated with changes in electrode impedance. The variability in response suggests that empirically derived transfer functions may be required to optimize the response of individual canals to a vestibular prosthesis, and that this function may need to be remapped over time. This article is part of a Special Issue entitled <Lasker Award>. | 25,245,586 | [
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Mental health state and quality of life questionnaire in low vision assessment: a case report. | Vision impairment associated with diabetic retinopathy, is well known and low vision rehabilitation is always recommended. In this report, the importance of objective measure of mental health and quality of life screening in diabetic retinopathy low-vision assessment is discussed. We describe the case of a 43-year-old Asian female who has mild vision impairment due to tractional retinal detachment secondary to diabetic retinopathy and how mental health screening and quality of life screening during low vision rehabilitation can improve in the management of this patient. Although vision impairment was mild, the psychological impact was enormous and affected her quality of life substantially. This case report illustrates that recognition of the mental health and quality of life impact on visual impairment is critical to the rehabilitation management of low vision patients with diabetic retinopathy. | 25,245,590 | [
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Emergence of rice yellow mottle virus in eastern Uganda: Recent and singular interplay between strains in East Africa and in Madagascar. | Epidemics of rice yellow mottle virus (RYMV) have developed recently in eastern Uganda, close to Lake Victoria in East Africa. Unexpectedly, all isolates from the affected area belonged to a single strain (named S4ug), a strain that is different from the S4lv strain that has been prevalent in the Lake Victoria basin for the past five decades. Interestingly, the S4ug strain is most closely related at the genomic level (except ORF1) to the strain present in Madagascar (S4mg), 2000km away. The minor parent of the S4mg recombinant strain could not be detected. Molecular clock dating analysis indicated that the singular sequence of events - that associated the emergence of a new strain (S4ug), a modular recombination between closely related strains (S4mg and S4ug) and a long distance transmission (S4mg) - occurred recently, within the past few decades. This finding is at variance with the process of gradual strain dispersal and diversification over two centuries throughout Africa that was previously established. | 25,245,592 | [
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Efficacy of endoscopic ultrasound-guided hemostatic interventions for resistant nonvariceal bleeding. | A subset of patients with nonvariceal gastrointestinal bleeding fail, or are unsuitable candidates for, endoscopic, radiologic, and surgical interventions. Endoscopic ultrasound (EUS)-guided intervention might be effective in these patients. We performed EUS-guided hemostatic interventions for 17 patients with nonvariceal gastrointestinal bleeding from June 2003 through May 2014 who failed, or were unsuitable candidates for, additional therapies. Indications for treatment included gastrointestinal stromal tumors, colorectal vascular malformations, duodenal masses or polyps, Dieulafoy lesions, duodenal ulcers, rectally invasive prostate cancer, pancreatic pseudoaneurysms, ulcerated esophageal cancer, and ulceration after Roux-en-Y gastric bypass. After the procedure, 88% of patients have had no further bleeding related to the treated lesion, over a median follow-up period of 12 months. EUS-guided hemostatic therapy therefore is feasible and useful for select patients with clinically severe, refractory, or recurrent nonvariceal gastrointestinal bleeding. | 25,245,627 | [
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Structure-function analysis of hepatitis C virus envelope glycoproteins E1 and E2. | Hepatitis C virus (HCV) is the leading cause of chronic liver disease in humans. The envelope proteins of HCV are potential candidates for vaccine development. The absence of three-dimensional (3D) structures for the functional domain of HCV envelope proteins [E1.E2] monomer complex has hindered overall understanding of the virus infection, and also structure-based drug design initiatives. In this study, we report a 3D model containing both E1 and E2 proteins of HCV using the recently published structure of the core domain of HCV E2 and the functional part of E1, and investigate immunogenic implications of the model. HCV [E1.E2] molecule is modeled by using aa205-319 of E1 to aa421-716 of E2. Published experimental data were used to further refine the [E1.E2] model. Based on the model, we predict 77 exposed residues and several antigenic sites within the [E1.E2] that could serve as vaccine epitopes. This study identifies eight peptides which have antigenic propensity and have two or more sequentially exposed amino acids and 12 singular sites are under negative selection pressure that can serve as vaccine or therapeutic targets. Our special interest is 285FLVGQLFTFSPRRHW299 which has five negatively selected sites (L286, V287, G288, T292, and G303) with three of them sequential and four amino acids exposed (F285, L286, T292, and R296). This peptide in the E1 protein maps to dengue envelope vaccine target identified previously by our group. Our model provides for the first time an overall view of both the HCV envelope proteins thereby allowing researchers explore structure-based drug design approaches. | 25,245,635 | [
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A bizarre parosteal osteochondromatous proliferation (Nora's lesion) of metatarsus, a histopathological and etiological puzzlement. | Nora's lesion (bizarre parosteal osteochondromatous proliferation) is a rare, benign lesion that is composed of differing amounts of cartilage, bone, and spindle cells and an unusual form of calcified cartilage so-called "blue bone". Whether it represents a reactive proliferation or a neoplastic lesion still remains controversial. We present a 24-year-old woman having a 4.5cm two lobulated mass attached to second metatarsus of her left foot. The lesion was hyperintense on magnetic resonance imaging and accompanied by an extensive soft tissue and bone marrow edema. In resection specimen, smaller lobule appeared stuck-on the cortex while the larger one had a broader base and a 0.4cm cartilaginous cap-like formation. The histological picture was best fit to Nora's lesion however showed less fibroblastic tissue and cartilaginous pleomorphism. The lesion also showed areas with cortical invasion and a small focus of fracture callus accompanied by adjacent medullary edema and fat necrosis. The case is presented with the comparative radiologic, macroscopic and microscopic findings for its diagnostic difficulties and etiopathogenetic considerations in favour of a maturation phenomenon in parosteal ostecartilaginous lesions irrespective of the cause. | 25,245,639 | [
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Causes and treatments of lag screw's cut out after intramedullary nailing osteosinthesis for trochanteric fractures. | Background. Superior cut-out of a lag screw remains a serious complication in the treatment of trochanteric or subtrochanteric fractures and it is related to many factors: the type of fracture, osteoporosis and the stability of fracture reduction. Little is known about the outcome after revision surgery for complications of the gamma nail. We assessed the outcome in patients who had revision surgery because of lag screw's cut out after gamma nailing for a trochanteric fracture.Material and Method. We present a study of 20 consecutive patients who underwent treatment after 20 cut-out of the lag screw fixation of a trochanteric fracture with Gamma Locking Nail from September 2004 to November 2010. In 16 patients hip prothesis was performed, in 1 the removal of the implant and in 3 the reosteosynthesis. We reviewed 13 patients: 10 total hip arthroplasty, 2 endoprothesis and 1 reosteosynthesis of nail and lag screw (mean follow up: 26 months, mean age: 73 years old), 7 patients died. Patients were reviewed retrospectively by an independent observer. Clinical evaluation was performed, Oxford score and Harris Hip score were measured. X-Ray examination was performed after a minimum of 12 months of follow up.Results. Mean Harris Hip Score mean was 67 and mean Oxford score was 32 in hip prothesis group (12 patients). We had several complications, Implant-related complications were: 2 ipometria &gt; 2cm, 2 recurrent hip arthroplasty dislocations (1 reoperated), 4 persistent thigh pain. In only 4 patients none complications were observed. Another patient, who had been subjected to reosteosinthesis, obtained better results (HHS:95, Oxford score:45) but with a 2 cm ipometria and occasional pain in the thigh.Conclusion. Cut out after gamma nail is consequent to biological or mechanical causes. Treatment of this complication is hip prosthesis (parzial or total hip arthroplasty), reosteosynthesis of the lag screw and/or the nail and the removal of the implant. Conversion to total/parzial hip arthroplasty may be a demanding operation with a higher complication rate respect to the standard, while reosteosynthesis is possible in selected patients and early cutting out. | 25,245,649 | [
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Results after revision of the stem in periprosthetic fractures of the hip. | Periprosthetic femoral fractures following primary total hip arthroplasty (THA) represent an emerging challenge for the orthopaedic surgeon, because of their increasing incidence and negative impact on clinical and functional patient outcome. For these reasons, in the last decade, many efforts were made to prevent and manage this complication and a large number of studies were focused on finding out the best treatment. The type of treatment depends on several factors such as morphology and location of the fracture, implant stability, quality and quantity of bone stock, patient's age and clinical conditions. Fractures that cause loosening of the stem always require its revision, with a contextual assessment of the quality and quantity of remaining bone stock, which is generally good in type B2 and poor in type B3 according to Vancouver's classification. The latter may require the use of bone grafts. In this context, the authors performed the following study and analyzed the results of 45 patients treated surgically for periprosthetic femoral fractures with revision of the femoral stem during a fourteen years period, between June 1999 and June 2013. | 25,245,651 | [
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Severe hypokalemia and hypophosphatemia presenting with carpopedal spasm associated with rhabdomyolysis. | Background Severe hypokalemia, defined as serum potassium &lt; 2.5 mEq/L, may lead to neuromuscular, gastrointestinal, and ECG abnormalities. Neuromuscular consequences of hypokalemia include weakness, cramps, rarely paralysis, eventually progressing to rhabdomyolysis. Case presentation We report a case of a 4-year-old girl presenting carpopedal spasm and rhabdomyolysis due to severe hypokalemia associated to hypophosphatemia and hypovolemia. At one month of age she underwent an ileal resection because of a neonatal necrotizing enterocolitis, and a bowel resection at two years of age, because of sub-occlusive episodes. The child had frequent episodes of diarrhoea and was treated with oral white clay (kaolin) and a restrictive diet. Three days prior the admission to the hospital she had numerous episodes of watery diarrhoea. Laboratory tests revealed severe hypokalemia, hypophosphatemia, normal calcium levels associated with marked dehydration. An ECG demonstrated sinus bradycardia, ST-segment depression, T-wave flattening, U-wave, and long-QTc. Symmetric carpal and pedal spasms were observed. A marked rise of creatinine phosphokinase and myoglobin associated to cola colored urine was observed. Intravenous supplementation of potassium phosphate as well as adequate volume repletion led to an improvement of the clinical condition, to the disappearance of carpal and pedal spasms, to normalisation of ECG. Conclusions Careful electrolytes and volume supplementation led to the correction of potential life-threatening arrhythmias and obtained a complete recovery from carpopedal spasm and rhabdomyolysis. Dietary restriction and pharmacological preparations as kaolin have to be administered with caution to treat diarrhea in children and particularly in those who may present other pre-existing risk factors. | 25,245,653 | [
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Using correlative light and electron microscopy to study zebrafish vascular morphogenesis. | Live imaging is extremely useful to characterize the dynamics of cellular events in vivo, yet it is limited in terms of spatial resolution. Correlative light and electron microscopy (CLEM) allows combining live confocal microscopy with electron microscopy (EM) for the characterization of biological samples at high temporal and spatial resolution. Here we describe a protocol allowing extracting endothelial cell ultrastructure after having imaged the same cell in its in vivo context through live confocal imaging during zebrafish embryonic development. | 25,245,685 | [
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Light sheet-based imaging and analysis of early embryogenesis in the fruit fly. | The fruit fly is an excellent model system for investigating the sequence of epithelial tissue invaginations constituting the process of gastrulation. By combining recent advancements in light sheet fluorescence microscopy (LSFM) and image processing, the three-dimensional fly embryo morphology and relevant gene expression patterns can be accurately recorded throughout the entire process of embryogenesis. LSFM provides exceptionally high imaging speed, high signal-to-noise ratio, low level of photoinduced damage, and good optical penetration depth. This powerful combination of capabilities makes LSFM particularly suitable for live imaging of the fly embryo.The resulting high-information-content image data are subsequently processed to obtain the outlines of cells and cell nuclei, as well as the geometry of the whole embryo tissue by image segmentation. Furthermore, morphodynamics information is extracted by computationally tracking objects in the image. Towards that goal we describe the successful implementation of a fast fitting strategy of Gaussian mixture models.The data obtained by image processing is well-suited for hypothesis testing of the detailed biomechanics of the gastrulating embryo. Typically this involves constructing computational mechanics models that consist of an objective function providing an estimate of strain energy for a given morphological configuration of the tissue, and a numerical minimization mechanism of this energy, achieved by varying morphological parameters.In this chapter, we provide an overview of in vivo imaging of fruit fly embryos using LSFM, computational tools suitable for processing the resulting images, and examples of computational biomechanical simulations of fly embryo gastrulation. | 25,245,688 | [
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Simulating tissue morphogenesis and signaling. | During embryonic development tissue morphogenesis and signaling are tightly coupled. It is therefore important to simulate both tissue morphogenesis and signaling simultaneously in in silico models of developmental processes. The resolution of the processes depends on the questions of interest. As part of this chapter we introduce different descriptions of tissue morphogenesi s. In the simplest approximation tissue is a continuous domain and tissue expansion is described according to a predefined function of time (and possibly space). In a slightly more advanced version the expansion speed and direction of the tissue may depend on a signaling variable that evolves on the domain. Both versions will be referred to as "prescribed growth." Alternatively tissue can be regarded as incompressible fluid and can be described with Navier-Stokes equations. Local cell expansion, proliferation, and death are then incorporated by a source term. In other applications the cell boundaries may be important and cell-based models must be introduced. Finally, cells may move within the tissue, a process best described by agent-based models. | 25,245,703 | [
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An apical left ventricular aneurysm rupture presenting as left breast mass 11 years after surgical repair. | Left ventricular (LV) pseudoaneurysm is a rare entity and, consequently, there is limited knowledge of the condition's natural history. The most frequent mode of presentation for LV pseudoaneurysm is heart failure with chest pain. However, the variable presentation of this condition requires a high index of suspicion for diagnosis. We report the case of a 75-year-old woman who had suffered an acute myocardial infarction 23 years previously, which resulted in a calcified LV apical aneurysm. Three weeks prior to being referred to our hospital, she was noted by her general practitioner to have a left-sided breast mass although mammography was negative. One week later, she attended the accident and emergency department; she was haemodynamically unstable but was resuscitated successfully. Contrast enhanced computed tomography showed a large haematoma located in the left chest wall communicating with the left ventricle. She underwent emergency cardiac surgical repair. On arrival at the intensive care unit following surgery, her haemodynamic status was unstable, and she deteriorated rapidly and died. With this report, we aim to raise the level of awareness for an apical LV pulsatile mass that could anatomically expand and present as a breast mass or tumour. An early diagnosis and timely surgical intervention is essential in order to achieve better outcomes and avoid detrimental complications. | 25,245,713 | [
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Delayed diagnosis in metastatic lesions of the foot. | Pedal acrometastases are a rare complication of disseminated malignancy. To date, there is little in the literature documenting their clinical course. Our large orthopaedic oncology database was used to review the clinical course of symptomatic pedal acrometastases. A total of 15 cases of pedal acrometastases were identified from 2,595 patients with metastases. The median age at presentation was 64.5 years (range: 14-83 years) and the median length of foot symptoms (predominantly pain and swelling) prior to diagnosis of metastasis was 16 weeks (range: 6-104 weeks). The median survival following diagnosis was 4.6 months (range: 2.3-104.5 months). This study suggests that 0.58% of all osseous metastases involve the foot, and that symptoms of foot pain and swelling are often misdiagnosed, leading to delays in treatment. A high index of suspicion is required to diagnose pedal acrometastases early, thereby allowing early treatment so that the patient's quality of life can be maintained prior to death. | 25,245,734 | [
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A retrospective case note review of laparoscopic versus open reversal of Hartmann's procedure. | First described in 1921, Hartmann's procedure is the gold standard treatment for complicated sigmoid diverticular disease. It is also used commonly for other causes of perforation of the large bowel. However, the reversal rate in the UK is much lower than in comparable countries, at only 18-22%. Furthermore, laparoscopic reversal (LRH) is used far less frequently than open reversal (ORH) despite evidence that a laparoscopic technique reduces patient morbidity and decreases patient recovery time. This retrospective case note review undertook an analysis of all the patients who had undergone Hartmann's procedure at two centres in Leeds Teaching Hospitals NHS Trust between February 2007 and February 2012. Out of 305 patients, 235 were identified and included in the analysis. Comparisons were then drawn between LRH and ORH groups. The reversal rate was 21%. Three-quarters (76%) were performed using an open technique, 20% were laparoscopic and 5% were converted to an open procedure. The mean hospital stay was longer for the ORH group (9.82 days, standard deviation [SD]: 5.85 days, 95% confidence interval [CI]: 2.99 days) than for the LRH group (7.29 days, SD: 4.65 days, 95% CI: 11.58 days) p=0.006). Seven ORH patients (21%) were reoperated but only one LRH patient (13%) had a reoperation at six months. Five factors were found to have a significant effect on the likelihood of reversal of Hartmann's procedure. The overall reversal rate for Hartmann's procedure remains low. Shorter hospital stays, lower 6-month reoperation rates and reduced 30-day complication rates are associated with LRH when compared with ORH. | 25,245,735 | [
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Cancer immunoprevention--the next frontier. | Cancer immunotherapy is a rapidly developing field, but limited in its success by a high tumor burden and immune tolerance. In contrast, immunoprevention has the potential to prevent cancer before the development of immune tolerance, and to prevent cancer recurrence in the setting of minimal residual disease. Although immunoprevention for viral-induced cancers has been successful in the setting of hepatitis B and human papillomavirus vaccination, primary prevention of nonviral-induced cancers is in its infancy. In contrast, prevention of cancer recurrence after adjuvant treatment (secondary prevention) is gaining steam. This review provides an overview of the scope of research in cancer immunoprevention over the last three years and directions for future research. | 25,245,763 | [
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A nomogram to predict disease-free survival after surgical resection of GIST. | Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Adjuvant imatinib therapy has resulted in improved disease-free survival (DFS) following resection of primary GIST. The aim of our study was to create a nomogram to predict DFS following resection of GIST. Using a multi-institutional cohort of patients who underwent surgery for primary GIST at 7 academic hospitals in the USA and Canada between January 1998 and December 2012, a multivariable Cox proportional hazards model predicting DFS was created using backward stepwise selection. A nomogram to predict DFS following surgical resection of GIST was constructed with the variables selected in the multivariable model. We tested nomogram discrimination by calculating the C-statistic and compared the nomogram to four existing GIST prognostic stratification systems. A total of 365 patients who underwent surgery for primary GIST was included in the study. Using backward stepwise selection, sex, tumor size, tumor site, and mitotic rate were selected for incorporation into the nomogram. The nomogram demonstrated superior discrimination compared to the NIH criteria, modified NIH criteria, and Memorial Sloan-Kettering Nomogram and had similar discrimination to the Miettinen criteria (C-statistic 0.77 vs 0.73, 0.71, 0.71, and 0.78, respectively). Four independent predictors of recurrence following surgery for primary GIST were used to create a nomogram to predict DFS. The nomogram stratified patients into prognostic groups and performed well on internal validation. | 25,245,766 | [
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The Reference Ability Neural Network Study: motivation, design, and initial feasibility analyses. | We introduce and describe the Reference Ability Neural Network Study and provide initial feasibility data. Based on analyses of large test batteries administered to individuals ranging from young to old, four latent variables, or reference abilities (RAs) that capture the majority of the variance in age-related cognitive change have been identified: episodic memory, fluid reasoning, perceptual speed, and vocabulary. We aim to determine whether spatial fMRI networks can be derived that are uniquely associated with the performance of each reference ability. We plan to image 375 healthy adults (50 per decade from age 20 to 50; 75 per decade from age 50 to 80) while performing a set of 12 cognitive tasks. Data on 174 participants are reported here. Three tasks were grouped a priori into each of the four reference ability domains. We first assessed to what extent both cognitive task scores and activation patterns readily show convergent and discriminant validity, i.e. increased similarity between tasks within the same domain and decreased similarity between tasks between domains, respectively. Block-based time-series analysis of each individual task was conducted for each participant via general linear modeling. We partialled activation common to all tasks out of the imaging data. For both test scores and activation topographies, we then calculated correlations for each of 66 possible pairings of tasks, and compared the magnitude of correlation of tasks within reference ability domains to that of tasks between domains. For the behavioral data, globally there were significantly stronger inter-task correlations within than between domains. When examining individual abilities, 3 of the domains also met these criteria but memory reached only borderline significance. Overall there was greater topographic similarity within reference abilities than between them (p<0.0001), but when examined individually, statistical significance was reached only for episodic memory and perceptual speed. We then turned to a multivariate technique, linear indicator regression analysis, to derive four unique linear combinations of Principal Components (PC) of imaging data that were associated with each RA. We investigated the ability of the identified PCs to predict the reference domain associated with the activation of individual subjects for individual tasks. Median accuracy rates for associating component task activation with a particular reference ability were quite good: memory: 82%; reasoning: 87%; speed: 84%; vocabulary: 77%. These results demonstrate that even using basic GLM analysis, the topography of activation of tasks within a domain is more similar than tasks between domains. The follow-up regression analyses suggest that all tasks with each RA rely on a common network, unique to that RA. Our ultimate goal is to better characterize these RA neural networks and then study how their expression changes across the age span. Our hope is that by focusing on these networks associated with key features of cognitive aging, as opposed to task-related activation associated with individual tasks, we will be able to advance our knowledge regarding the key brain changes that underlie cognitive aging. | 25,245,813 | [
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[Ovulation induction by pulsatile GnRH therapy in 2014: literature review and synthesis of current practice]. | The hypogonadotropic hypogonadism is an easily treatable form of female infertility. The most common cause of hypogonadotropic hypogonadism is functional hypothalamic amenorrhea. The GnRH pump is a simple and effective treatment to restore fertility of patients with hypothalamic amenorrhea: cumulative pregnancy rate is estimated between 70 and 100% after 6 cycles, compared to a low rate of complications and multiple pregnancies. While only 2.8 cycles are on average required to achieve a pregnancy with a pump, this induction of ovulation stays underused in France. The objective of this paper is to propose a practical manual of pulsatile GnRH, in order to improve the accessibility of pulsatile GnRH for patients with hypogonadotropic hypogonadism. | 25,245,838 | [
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Optical magnification devices in tonsillectomy: a prospective randomised clinical study. | Tonsillectomy is one of the most common surgical procedure in otorhinolaryngology. A plethora of approaches has been undertaken so far to limit postoperative pain, one of the major problems patients are concerned with. Thermal damages of the surrounding tissue caused by coagulation during surgery are discussed to correlate with postoperative pain. Therefore, we studied whether the use of magnification devices reduced coagulation procedures and consequently limited post-operative pain. Following an intraindividual design, we performed tonsillectomy on one side using a microscope or magnifying glasses whereas the opposite side was operated with unsupported vision. As verified by a visual analogue scale, our study shows that neither the use of a microscope, nor the use of magnifying glasses leads to less post-operative pain. Other parameters like post-operative bleeding, duration of surgery, and total applied energy by bipolar coagulation were also comparable in the different treatment groups. Taken together, magnification-supported tonsillectomy does not seem to be appropriate for limiting complications of tonsillectomy, especially not for reducing post-operative pain. | 25,245,863 | [
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Medially placed vagus nerve in relation to common carotid artery: a pointer to a non-recurrent laryngeal nerve. | The aim of this study was to highlight a medialized vagus in relation to common carotid artery as an operative marker to a non-recurrent laryngeal nerve during thyroid surgeries. Three patients who underwent thyroidectomy, in who per operative diagnosis of right non-recurrent laryngeal nerve was made and the findings were confirmed radiologically by demonstration of aberrant subclavian artery were included in the study. A medially placed vagus nerve in relation to common carotid artery was the common observation in all the 3 patients. With no operative marker to identify a non-recurrent laryngeal nerve, it is more prone to injury during thyroidectomies. Vagus nerve which was constantly seen medial to the common carotid artery in all our three patients can be used as an operative marker to a non-recurrent laryngeal nerve. | 25,245,864 | [
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Long-term vascular contractility assay using genipin-modified muscular thin films. | Vascular disease is a leading cause of death globally and typically manifests chronically due to long-term maladaptive arterial growth and remodeling. To date, there is no in vitro technique for studying vascular function over relevant disease time courses that both mimics in vivo-like tissue structure and provides a simple readout of tissue stress. We aimed to extend tissue viability in our muscular thin film contractility assay by modifying the polydimethylsiloxane (PDMS) substrate with micropatterned genipin, allowing extracellular matrix turnover without cell loss. To achieve this, we developed a microfluidic delivery system to pattern genipin and extracellular matrix proteins on PDMS prior to cell seeding. Tissues constructed using this method showed improved viability and maintenance of in vivo-like lamellar structure. Functional contractility of tissues fabricated on genipin-modified substrates remained consistent throughout two weeks in culture. These results suggest that muscular thin films with genipin-modified PDMS substrates are a viable method for conducting functional studies of arterial growth and remodeling in vascular diseases. | 25,245,868 | [
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[Review of the novelties presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (II)]. | The most relevant data presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in October 2013 in Denmark, were summarised at the sixth edition of the Post-ECTRIMS Expert Meeting, held in Madrid in October 2013, resulting in this review, which is being published in three parts. This second part of the Post-ECTRIMS review focuses on diagnostic imaging and differential diagnosis, the clinical and paraclinical monitoring of neurodegeneration, progression and disability, and functional imaging and neural connectivity. It is clear that conventional multiple sclerosis sequences remain essential for the diagnosis, differential diagnosis and disease monitoring, that new MRI techniques help to assess the neurodegenerative process, and that some of the new sequences are more specific to neuroaxonal injury. Very high field magnetic resonance imaging allows better understanding of the lesion load, distribution and heterogeneity of the lesions, and positron emission tomography studies offer new insight into the patho-physiology of the disease. Functional imaging and neural connectivity studies show that there is cortical reorganisation in multiple sclerosis, whose equilibrium with structural damage is responsible for the impairment. | 25,245,875 | [
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Extensive thoracolumbosacral vertebral osteomyelitis after Lemierre syndrome. | To present a unique case of multilevel vertebral osteomyelitis after Lemierre syndrome. A previously healthy 27-year-old man presented in the Emergency Department in septic shock because of Lemierre syndrome for which he was subsequently treated with intravenous benzylpenicillin for 2 months. Two and a half months later, the patient was readmitted with severe back pain without neurological deficits or fever. Imaging revealed an extensive vertebral osteomyelitis of the complete thoracic, lumbar and sacral spine. Although the blood cultures obtained at the initial admission for Lemierre syndrome revealed Fusobacterium species and Streptococcus milleri, the cultures from the spinal biopsies remained negative. Histology of the spinal biopsies showed a purulent sclerosing osteomyelitis. The patient was successfully treated with intravenous piperacillin and tazobactam. Despite persisting back pain, no recurrence of infection was seen at 3 years of follow-up. Lemierre syndrome and an extensive thoracolumbosacral vertebral osteomyelitis are rare but serious infections. Clinicians must maintain a high index of suspicion for infectious metastases leading to vertebral osteomyelitis when a patient presents with back pain after an episode of life-threatening septicaemia caused by Lemierre syndrome. | 25,245,891 | [
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Solution mechanism guide: implementing innovation within a research & development organization. | In order to create a culture more open to novel problem-solving mechanisms, NASA's Human Health and Performance Directorate (HH&P) created a strategic knowledge management tool that educates employees about innovative problem-solving techniques, the Solution Mechanism Guide (SMG). The SMG is a web-based, interactive guide that leverages existing and innovative problem-solving methods and presents this information as a unique user experience so that the employee is empowered to make the best decision about which problem-solving tool best meets their needs. By integrating new and innovative methods with existing problem solving tools, the SMG seamlessly introduces open innovation and collaboration concepts within HH&P to more effectively address human health and performance risks. This commentary reviews the path of creating a more open and innovative culture within HH&P and the process and development steps that were taken to develop the SMG. | 25,245,908 | [
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[Management of brain abscesses in era of computed tomography in sub-Saharan Africa: a review of 112 cases]. | The authors report a retrospective study conducted on 112 cases of cerebral abscesses collected over a period of 12 years from the medical records of the department of neurosurgery at the Yalgado Ouedraogo university teaching hospital, Ouagadougou-Burkina Faso. The analyses were conducted on the epidemiological, clinical and prognostic aspects of the cases. The mean age of the patients (73 men and 39 women) was 26 years. The primary mode of infection ranged from cranial injuries (25%) to meningitis (17.9%) and sinusitis (15.2%). Bacteria were isolated from 16.1% cases; staphylococci and streptococci were the most frequent bacteria identified. The main clinical symptoms were motor deficit (75.9%), fever (74.1%) and headache (66.1%). Diagnosis was performed by CT scan in all cases. Fifty-three patients were treated using antibiotics alone; this medical treatment was completed by surgery in 59 cases. The results showed that 37.5% of the patients in fact fully recovered while some sequelae were identified in 49.1%. The mortality rate was 13.4%. Consciousness disorders were in most cases responsible for the patient's death. Moreover multiple and/or voluminous abscesses were factors of the poor functional prognosis. Due to the high mortality rate and the frequency of sequelae, the authors emphasize the need of prevention by using adequate and sufficient antibiotics during primary infections. | 25,245,921 | [
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Iron and copper in male reproduction: a double-edged sword. | Iron and copper are essential trace nutrients playing important roles in general health and fertility. However, both elements are highly toxic when accumulating in large quantities. Their direct or indirect impact on the structure and function of male gonads and gametes is not completely understood yet. Excess or deficiency of either element may lead to defective spermatogenesis, reduced libido, and oxidative damage to the testicular tissue and spermatozoa, ultimately leading to fertility impairment. This review will detail the complex information currently available on the dual roles iron and copper play in male reproduction. | 25,245,929 | [
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Creativity and the default network: A functional connectivity analysis of the creative brain at rest. | The present research used resting-state functional magnetic resonance imaging (fMRI) to examine whether the ability to generate creative ideas corresponds to differences in the intrinsic organization of functional networks in the brain. We examined the functional connectivity between regions commonly implicated in neuroimaging studies of divergent thinking, including the inferior prefrontal cortex and the core hubs of the default network. Participants were prescreened on a battery of divergent thinking tests and assigned to high- and low-creative groups based on task performance. Seed-based functional connectivity analysis revealed greater connectivity between the left inferior frontal gyrus (IFG) and the entire default mode network in the high-creative group. The right IFG also showed greater functional connectivity with bilateral inferior parietal cortex and the left dorsolateral prefrontal cortex in the high-creative group. The results suggest that the ability to generate creative ideas is characterized by increased functional connectivity between the inferior prefrontal cortex and the default network, pointing to a greater cooperation between brain regions associated with cognitive control and low-level imaginative processes. | 25,245,940 | [
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Strong DNA deformation required for extremely slow DNA threading intercalation by a binuclear ruthenium complex. | DNA intercalation by threading is expected to yield high affinity and slow dissociation, properties desirable for DNA-targeted therapeutics. To measure these properties, we utilize single molecule DNA stretching to quantify both the binding affinity and the force-dependent threading intercalation kinetics of the binuclear ruthenium complex Δ,Δ-[μ-bidppz-(phen)4Ru2]4+ (Δ,Δ-P). We measure the DNA elongation at a range of constant stretching forces using optical tweezers, allowing direct characterization of the intercalation kinetics as well as the amount intercalated at equilibrium. Higher forces exponentially facilitate the intercalative binding, leading to a profound decrease in the binding site size that results in one ligand intercalated at almost every DNA base stack. The zero force Δ,Δ-P intercalation Kd is 44 nM, 25-fold stronger than the analogous mono-nuclear ligand (Δ-P). The force-dependent kinetics analysis reveals a mechanism that requires DNA elongation of 0.33 nm for association, relaxation to an equilibrium elongation of 0.19 nm, and an additional elongation of 0.14 nm from the equilibrium state for dissociation. In cells, a molecule with binding properties similar to Δ,Δ-P may rapidly bind DNA destabilized by enzymes during replication or transcription, but upon enzyme dissociation it is predicted to remain intercalated for several hours, thereby interfering with essential biological processes. | 25,245,944 | [
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Surviving cutaneous melanoma: a clinical review of follow-up practices, surveillance, and management of recurrence. | The number of melanoma survivors in the United States continues to steadily increase 2.6% per year, while death rates have remained stable over time. Although controversy exists regarding optimal surveillance strategies, recommendations for clinical monitoring are based on tumor stage, tumor phenotype, likelihood of recurrence, prognosis, risk factors, psychosocial impact of disease, and patient well-being. Management guidelines for recurrent disease depend on the type of recurrence: local, satellite/in-transit, regional, or distant metastasis. This article is a current review of the literature concerning melanoma survivorship. | 25,245,963 | [
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Sitafloxacin: antimicrobial activity against ciprofloxacin-selected laboratory mutants of Mycoplasma genitalium and inhibitory activity against its DNA gyrase and topoisomerase IV. | A sitafloxacin regimen is highly effective on Mycoplasma genitalium infections, including those caused by the mycoplasmas harboring mutant topoisomerase IV with a quinolone resistance-associated amino acid change in ParC. In this study, we evaluated sitafloxacin antimicrobial activities against M. genitalium, including the mycoplasmas with decreased susceptibilities to quinolones, by determining minimum inhibitory concentrations (MICs) for the strain ATCC 33530 and its 3 ciprofloxacin-selected mutants, for which ciprofloxacin MICs were 8-16 times higher than that for their parent strain. We also evaluated inhibitory activities against the target enzymes of M. genitalium by determining concentrations required to inhibit 50% (IC50) of the supercoiling activity of the recombinant wild-type DNA gyrase and the decatenating activities of the recombinant wild-type topoisomerase IV and the 2 types of mutant topoisomerase IV with a single amino acid change in ParC. Sitafloxacin MICs were 0.125 for the parent strain and 0.125-0.25 μg/ml for the mutants. Sitafloxacin IC50s were 3.12 for the supercoiling activity of the wild-type DNA gyrase and 2.98 μg/ml for the decatenating activity of the wild-type topoisomerase IV. Its IC50s for the decatenating activity of the mutant topoisomerase IV harboring an amino acid change in ParC were 15.1 for Gly-81 → Cys and 7.92 μg/ml for Asp-87 → Tyr. Sitafloxacin was highly active against ciprofloxacin-selected mutants of M. genitalium and possessed intense inhibitory activities not only against wild-type DNA gyrase and topoisomerase IV but also against mutant topoisomerase IV containing ParC with a quinolone resistance-associated amino acid change. Sitafloxacin could be a promising agent for M. genitalium infections. | 25,245,990 | [
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Do fish perceive illusory motion? | Motion illusion refers to a perception of motion that is absent or different in the physical stimulus. These illusions are a powerful non-invasive tool for understanding the neurobiology of vision because they tell us, indirectly, how we process motion. There is general agreement in ascribing motion illusion to higher-level processing in the visual cortex, but debate remains about the exact role of eye movements and cortical networks in triggering it. Surprisingly, there have been no studies investigating global illusory motion evoked by static patterns in animal species other than humans. Herein, we show that fish perceive one of the most studied motion illusions, the Rotating Snakes. Fish responded similarly to real and illusory motion. The demonstration that complex global illusory motion is not restricted to humans and can be found even in species that do not have a cortex paves the way to develop animal models to study the neurobiological bases of motion perception. | 25,246,001 | [
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Vaccine resource tracking systems. | From 1999 to 2010, annual disbursements of development assistance for health for vaccinations increased from $0.5 billion to $2.0 billion (all financial values USD 2010). In its 2012 Global Vaccine Action Plan (GVAP), the World Health Assembly recommended establishing a comprehensive vaccination resource tracking system to better understand the source and recipients of these funds, and ultimately their impact on outcomes. This systematic review aims to respond to the GVAP recommendation in reviewing and assessing the state of the data and literature on vaccination resource tracking. We scrutinized all relevant vaccination resource tracking systems identified in the literature and by practitioners in the field. We examined schemes used elsewhere in the health sector and by other sectors. Informant interviews were also conducted to determine what data exists and how it might be utilized. With this information, we completed a qualitative assessment of existing approaches to vaccination resources tracking. Tracking systems provide information about some vaccine-related activity in the majority of low- and middle-income countries. Data are generally available for the period of 2006-2010. Levels of granularity vary. Interviewees were concerned about the degree of rigor used to validate the data and the lack of verification. Data are often presented in tabular form, which may be unwieldy for non-technical audiences. The schemes currently in place to track the resources available for vaccinations were fairly advanced relative to other mechanisms in the health sector. Nonetheless, the coverage, validity, and accessibility of vaccination resource tracking data could be ameliorated. Establishing improved feedback loops and verification mechanisms that connect country-level administrators and the international organizations that support reporting efforts would enhance data quality. | 25,246,005 | [
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Benzodiazepine modulation of homomeric GABAAρ1 receptors: differential effects of diazepam and 4'-chlorodiazepam. | GABA(A) receptors (GABA(A)Rs) are ligand-gated ion channels that mediate inhibitory neurotransmission in the central nervous system (CNS). They are members of the Cys-loop receptor family and display marked structural and functional heterogeneity. Many GABA(A)Rs receptor subtypes are allosterically modulated by benzodiazepines (BDZs), which are drugs extensively used as anxiolytics, sedative-hypnotics and anticonvulsants. One high-affinity site and at least three additional low-affinity sites for BDZ recognition have been identified in several heteromeric and homomeric variants of the GABA(A)Rs (e.g.: α1β2γ2, α1β2/3, β3, etc.). However, the modulation of homomeric GABA(A)ρRs by BDZs was not previously revealed, and these receptors, for a long a time, were assumed to be fully insensitive to the actions of these drugs. In the present study, human homomeric GABA(A)ρ1 receptors were expressed in Xenopus oocytes and GABA-evoked responses electrophysiologically recorded in the presence or absence of BDZs. GABA(A)ρ1 receptor-mediated responses were modulated by diazepam and 4'-chlorodiazepam in the micromolar range, in a concentration-dependent, voltage-independent and reversible manner. Diazepam produced potentiating effects on GABA-evoked Cl(-) currents and 4'-Cl diazepam induced biphasic effects depending on the GABA concentration, whereas Ro15-4513 and alprazolam were negative modulators. BDZ actions were insensitive to flumazenil. Other BDZs showed negligible activity at equivalent experimental conditions. Our results suggest that GABA(A)ρ1 receptor function can be selectively and differentially modulated by BDZs. | 25,246,015 | [
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The role of heparan sulfate as determining pathogenic factor in complement factor H-associated diseases. | Complement factor H (FH) systemically inhibits excessive complement activation in the microenvironment of host cells, but for instance not on microbes. This self-recognition is mediated by two binding sites that recognize distinctly sulfated heparan sulfate (HS) domains. The interaction with HS not only concentrates FH on host cells, but directly affects its activity, evoking novel models of conformational activation. Genetic aberrations in the HS-binding domains systemically disturb the protective function of FH, yet the resulting loss of complement control affects mainly ocular and renal tissues. Recent results suggest that the specific expression of HS domains in these tissues restricts the interaction of HS to a single binding site within FH. This lack of redundancy could predispose eyes and kidneys to complement-mediated damage, making HS a central determinant for FH-associated diseases. | 25,246,018 | [
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Total loss of Teeth in Adults, United States - 1960-1962. | Estimates of the prevalence and distribution of edentulous persons-men and women who have lost all of their natural teeth-are in essence statistical summaries reflecting both the amount and extent of dental disease and the failure to obtain prompt and adequate dental care. Toothdecay and periodontal disease-a degenerative process which affects the structures that support the teeth- are, without question, the two leading causes of tooth loss. It is also true that both disorders are extremely prevalent throughout the United States. When treatment is not delayed too long, however, either can usually be arrested by the skills and methods commanded by most dentists. Failing that, tooth removal is a harsh but inescapable consequence which culminates for many men and women in the loss of all natural teeth. The first estimates which presented in true perspective the magnitude and extent of total tooth loss throughout the United States were published in 1960. The estimates were based on responses to the following question which was asked during 1957-58 at approximately 36,000 households comprising about 115,000 people: "Is there anyone in the family who has lost all of his teeth?" Responses from the interviewed households indicated that about 22 million people-13 percent of the Nation's population had indeed lost all of their permanent teeth. The existence of significant, nationwide trends associated with various demographic characteristics was also clearly revealed. The prevalence of total tooth loss which, as expected, mounted rapidly with age was higher among women than among men, higher among white than among Negro adults, and higher among poorer and less educated people than among more advantaged ones. In addition, some variation in prevalence by region appeared in the estimates. No difference in prevalence associated with population density was found. | 25,246,034 | [
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Behavior problems and timing of menarche: a developmental longitudinal biometrical analysis using the NLSY-Children data. | A powerful longitudinal data source, the National Longitudinal Survey of Youth Children data, allows measurement of behavior problems (BP) within a developmental perspective linking them to menarcheal timing (MT). In a preliminary analysis, we evaluate the bivariate relationships between BP measured at different developmental periods and the timing of menarche. Correlations were not consistent with any correlational/causal relationship between BP and MT. In the major part of our study, MT was used to moderate the developmental trajectory of BP, within a genetically-informed design. Girls reaching menarche early had behavior problem variance accounted for by the shared environment; those reaching menarche with average/late timing had behavior problem differences accounted for by genetic variance. Our findings match previous empirical results in important ways, and also extend those results. A theoretical interpretation is offered in relation to a theory linking genetic/shared environmental variance to flexibility and choices available within the family in relation to BP. | 25,246,040 | [
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Value of imaging in head and neck tumors. | In this review, the value of imaging in the management of head and neck tumors is summarized. The many diverse tumors of the head and neck are grouped for purposes of staging and treatment. The groupings of malignancies consist of sinonasal, nasopharynx, salivary gland, oral cavity, oropharynx, hypopharynx, larynx, and thyroid tumors. The anatomy, rationale for choice of imaging modality, interpretation of acquired images, staging, treatment options, and posttherapy assessment are discussed. | 25,246,046 | [
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Image-guided interventions in oncology. | Interventional oncology, a term commonly used to indicate the minimally invasive procedures performed by interventional radiologists to diagnose and manage cancer, encompasses a broad spectrum of techniques unique to interventional radiology that have been established as a vital part of the multidisciplinary oncologic cancer care team. This article provides an updated overview of the variety of applications of image-guided procedures to distinct clinical scenarios, such as the diagnosis, treatment, and management of complications of malignancies. | 25,246,055 | [
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Inhibitory effects of scutellarein on proliferation of human lung cancer A549 cells through ERK and NFκB mediated by the EGFR pathway. | High expression levels of cyclooxygenase-2 (COX-2) contribute a strong proliferative ability to human lung cancer cells, and this function is link to the epidermal growth factor receptor (EGFR) pathway, which was mediated by extracellular-signal-regulated kinase (ERK) and nuclear factor kappa B (NFκB). In this study, scutellarein, a flavonoid compound, was screened for proliferation inhibition at different concentrations (0, 5, 25 and 50 μM) at 24 h or 48 h in human lung cancer cell line A549. Results showed that A549 cell proliferation was inhibited by 50 μM scutellarein treatment in 24 h and 48 h of treatment. The expression levels of phosphorylated EGFR, phosphorylated ERK, phosphorylated NFκB and COX-2 were reduced in a dose-dependent manner after 24 h scutellarein treatments at different concentrations. Further, ERK inhibitor U0126 and NFκB inhibitor MG132 also inhibited A549 cell proliferation similar to 50 κM scutellarein treatment from 24 h to 48 h. The experimental results showed that scutellarein could inhibit proliferation of the human lung cancer cell line A549 through ERK and NFκB mediated by the EGFR pathway. | 25,246,059 | [
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S-adenosyl-l-methionine protection of acetaminophen mediated oxidative stress and identification of hepatic 4-hydroxynonenal protein adducts by mass spectrometry. | Acetaminophen (APAP) hepatotoxicity is protected by S-adenosyl-l-methionine (SAMe) treatment 1hour (h) after APAP in C57/Bl6 mice. This study examined protein carbonylation as well as mitochondrial and cytosolic protein adduction by 4-hydroxynonenal (4-HNE) using mass spectrometry (MS) analysis. Additional studies investigated the leakage of mitochondrial proteins and 4-HNE adduction of these proteins. Male C57/Bl6 mice (n=5/group) were divided into the following groups and treated as indicated: Veh (15ml/kg water, ip), SAMe (1.25mmol/kg, ip), APAP (250mg/kg), and SAMe given 1h after APAP (S+A). APAP toxicity was confirmed by an increase (p<0.05) in plasma ALT (U/l) and liver weight/10g body weight relative to the Veh, SAMe and S+A groups 4h following APAP treatment. SAMe administered 1h post-APAP partially corrected APAP hepatotoxicity as ALT and liver weight/10g body weights were lower in the S+A group compared the APAP group. APAP induced leakage of the mitochondrial protein, carbamoyl phosphate synthase-1 (CPS-1) into the cytosol and which was reduced in the S+A group. SAMe further reduced the extent of APAP mediated 4-HNE adduction of CPS-1. MS analysis of hepatic and mitochondrial subcellular fractions identified proteins from APAP treated mice. Site specific 4-HNE adducts were identified on mitochondrial proteins sarcosine dehydrogenase and carbamoyl phosphate synthase-1 (CPS-1). In summary, APAP is associated with 4-HNE adduction of proteins as identified by MS analysis and that CPS-1 leakage was greater in APAP treated mice. SAMe reduced the extent of 4-HNE adduction of proteins as well as leakage of CPS-1. | 25,246,065 | [
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Het effect van galantamine op de ecg- geleidingstijden. | Galantamine, one of the acethylcholinesterase inhibitors (AChEI), is used in the treatment of Alzheimer's disease. However AChEI have been associated with adverse events, including cardiac events. The objective of this prospective, observational study is to evaluate the association between galantamine and incident cardiac conduction abnormalities. A total of 64 patients, who visited an out - patient clinic of a geriatric department were enrolled in the study. All patients were diagnosed with Alzheimer's disease and started with a capsule containing 8 mg of galantamine. Subsequently, if galantamine was well tolerated, the dosage was raised every 4 weeks, to an eventual dosage of 24 mg/ day. The mean follow - up period was 4 months. ECG parameters were evaluated at baseline and after start of galantamine at each galantamine dose level (8, 16, 24 mg / day). No significant differences in electrocardiographic measurements before and during treatment with galantamine were found. No significant changes in ECG parameters relative to baseline were found with galantamine treatment. Also after adjustment for concomitant cardioactive medications and cardiovascular comorbidity, no significant changes were found. | 25,246,067 | [
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Phase resetting for a network of oscillators via phase response curve approach. | The problem of phase regulation for a population of oscillating systems is considered. The proposed control strategy is based on a phase response curve (PRC) model of an oscillator (the first-order reduced model obtained for linearized system and inputs with infinitesimal amplitude). It is proven that the control provides phase resetting for the original nonlinear system. Next, the problem of phase resetting for a network of oscillators is considered when applying a common control input. Performance of the obtained solutions is demonstrated via computer simulation for three different models of circadian/neural oscillators. | 25,246,107 | [
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Asymptomatic adenomyosis and embryo implantation in IVF cycles. | Research on the effect of adenomyosis on the rate of success of IVF is controversial. Differences in study design, study power, criteria and instrument used to diagnose adenomyosis and choice of controls may explain these discrepancies. To establish whether embryo implantation is impaired in women with adenomyosis, women scheduled for IVF were prospectively evaluated for the presence of adenomyosis and whether this condition affected embryo implantation. Forty-nine women with adenomyosis diagnosed at transvaginal ultrasound with no abnormal uterine bleeding were recruited. They were matched for study period, age, day of embryo transfer and number of transferred embryos to 49 controls without the disease. In women with adenomyosis, 24 out of 76 embryos transferred implanted (32%); this occurred in 16 out of 76 (21%) in unaffected controls. The crude odds ratio of implantation in affected women was 1.73 (95% CI 0.83 to 3.60). The odds ratio adjusted for body mass index (the unique variable found to differ at univariate analysis) was 1.78 (95% CI 0.85 to 3.77). In conclusion, implantation rate is not impaired in asymptomatic women who are diagnosed with adenomyosis at transvaginal sonography. Affected women can be reassured about the effect of this condition on their chances of success. | 25,246,118 | [
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The effects of liraglutide on male fertility: a case report. | Liraglutide is an agonist of the glucagon-like peptide I receptor, and is commonly recommended as a treatment for obesity and type 2 diabetes mellitus. Adverse effects related to liraglutide include acute pancreatitis and polyarthritis. No studies, however, have reported an adverse effect of liraglutide on male reproduction. This case report shows a deleterious effect of liraglutide on male reproductive function. | 25,246,122 | [
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Effect of cognitive intervention on children with ADHD. | Although not considered a diagnostic criterion in DSM-IV, motor difficulties in children with Attention Deficit Hyperactivity Disorder (ADHD) are commonly reported. Prevalence of co-morbidity of ADHD and Developmental Coordination Disorder is as high as 50%. Cognitive Orientation to daily Occupational Performance (CO-OP) is a problem-solving approach originally developed for children with Developmental Coordination Disorder. In this approach, therapists support children to use cognitive strategies in a process of guided discovery to solve occupational performance problems. A single case experimental design (multiple baselines) was used to examine the influence of a 12-week intervention using CO-OP with six children with ADHD. Outcome measures included the Canadian Occupational Performance Measure (COPM), Goal Attainment Scaling and the Bruininks-Oseretsky Test of Motor Proficiency and Performance (BOTMP). The results of this study demonstrated improvements in both goals and motor performance in the participants due to the intervention. These results provide some support for the use of CO-OP with children with ADHD. Further research into the application of CO-OP with children with ADHD is warranted based on these preliminary positive findings regarding the efficacy of this intervention to address motor-based performance difficulties. | 25,246,134 | [
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How I do it: combined direct (STA-MCA) and indirect (EDAS) EC-IC bypass. | EC-IC bypass for the treatment of a hypoperfused hemisphere is currently the treatment of choice for symptomatic moyamoya patients. Use of the combination of direct (STA-MCA) and indirect (an STA branch lay-on bypass and flipped dural flaps; EDAS) EC-IC bypass is advocated as the optimal treatment option as it allows immediate augmentation of flow in the postoperative period while allowing the brain to acquire additional indirect flow in the long term. We describe the technical nuances of a combined direct and indirect bypass in a 41-year-old woman with moyamoya syndrome diagnosed with transient ischemic attacks (TIAs) and cognitive decline. Combined direct and indirect bypass option should become a familiar treatment modality among vascular neurosurgeons. (1) Pay critical attention to not injuring the Superficial Temporal Artery, Parietal branch (STApb) while turning the skin incision anteriorly. Use the operating microscope to dissect the STApb. (2) Always mark the origin of the Superficial Temporal Artery, Frontal branch (STAfb) on the skin so that its location can be anticipated during STApb dissection. (3) When no frontal branch is available or if the frontal branch is of poor quality, the STApb can be used as a direct or indirect graft. (4) A craniotomy should be done 2-3 cm posterior to the course of the STApb to allow for adequate exposure for an indirect graft. (5) Manipulation of the donor vessels should be done with extreme care as spasm of the artery or intraluminal thrombosis may occur. Low cut flow in the direct graft should be interpreted with caution as vasospasm can result in significant temporary reduction of flow. (6) Aggressive distal dissection of the direct donor is a must. The distal 1-2 cm of the vessel should be cleaned of any loose tissue and be fishmouthed prior to anastomosis. (7) A blood-free field is mandatory. Perforators on the backside of the recipient should be sacrificed and cut to avoid backbleeding into the anastomotic segment during temporary occlusion. (8) When recirculating after the anastomosis has been completed, open the temporary clips on the recipient first. Backflow into the donor segment confirms a patent anastomosis. (9) Utilization of intraoperative angiography is not necessary as long as one utilizes flow measurements and ICG angiography. (10) Take great care with the bone flap reconstruction and the skin closure as the grafts can easily be compressed or sutured. Create a generous craniectomy in the bone flap to avoid any graft compression. | 25,246,144 | [
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Variability in target delineation for cavernous sinus meningioma and anaplastic astrocytoma in stereotactic radiosurgery with Leksell Gamma Knife Perfexion. | Radiosurgery clinical practice relays on empirical observations and the experience of the practitioners involved in determining and delineating the target and therefore variability in target delineation might be expected for all the radiosurgery approaches, independent of the technique and the equipment used for delivering the treatment. The main aim of this study was to quantify the variability of target delineation for two radiosurgery targets expected to be difficult to delineate. The secondary aim was to investigate the dosimetric implications with respect to the plan conformity. The primary aim of the study has therefore a very general character, not being bound to one specific radiosurgery technique. Twenty radiosurgery centers were asked to delineate one cavernous sinus meningioma and one astrocytoma and to plan the treatments for Leksell Gamma Knife Perfexion. The analysis of the delineated targets was based on the calculated 50 % agreement volume, AV50. The AV50 was compared to each delineated target by the concordance index and discordance index. The differences in location, size, and shape of the delineated targets were also analyzed using the encompassing volume compared to the common volume, i.e., the AV100, of all delineated structures. Target delineation led to major differences between the participating centers and therefore the AV50 was small in comparison to each delineated target volume. For meningioma, the AV50 was 5.90 cm(3), the AV100 was 2.60 cm(3), and the encompassing volume was 13.14 cm(3). For astrocytoma, the AV50 was 2.06 cm(3) while the AV100 was extremely small, only 0.05 cm(3), and the encompassing volume was 43.27 cm(3). These variations translate into corresponding discrepancies in plan conformity. Significant differences in shape, size, and location between the targets included in this study were identified and therefore the clinical implications of these differences should be further investigated. | 25,246,145 | [
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Metabolic syndrome - dysregulation of adipose tissue endocrine function. | Metabolic syndrome, acondition increasing cardiovascular morbidity, mortality and risk for diabetes mellitus type 2, is currently worldwide reaching epidemic proportions. This complex disorder represents an urgent challenge for new pharmacotherapeutic strategies formulation. Pathophysiological mechanisms underlying metabolic syndrome are not completely understood, nevertheless growing evidence is supporting the hypothesis that multiple metabolic dysregulations do contribute to its development. Apotential target for pharmacological intervention is considered to be dysregulation of adipose tissue endocrine/paracrine function. Specific adipokines, proteins secreted by the adipose tissue, with some pleiotropic effects, have been identified with strong association to regulation of energy metabolism, appetite, insulin signaling, tissue insulin sensitivity and the proinflammatory state related to metabolic syndrome. The aim of this paper is to provide a brief overview of endocrine/paracrine functions of the adipose tissue with regard to metabolic syndrome development and pathophysiology and particular adipokines as potential targets for innovative pharmacotherapeutic approaches. | 25,246,153 | [
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[Long-term adaptation of the patients to electrical stimulation in the course of rehabilitation following cochlear implantation]. | The objective of the present work was to study long-term adaptation of the patients to electrical stimulation in the course of rehabilitation following cochlear implantation. The following parameters were determined: variations of threshold auditory sensation of electrical stimulation (ESS), alteration of the maximum electrical stimulation comfort level (MCL), changes in the dynamic range (DR) of the stimulus and changes in the threshold auditory nerve action potentials (ANAP). The observations on ESS dynamics and DR of the stimulus were collected during 2 years after the first connection of the processor in a group of 27 patients. The data obtained from the 3rd, 12th, and 20th stimulation channels were included in the study. The observations on ANAP dynamics were collected during 1 year after surgery in a group of 112 patients. It was shown that ESS variations largely occurred within the first two weeks after connection and did not reach statistical significance. In contrast, MCL and DR changes showed a stably increasing tendency throughout the entire period of observations, with the enhancement of MCL of DR amounting to 25-28% and roughly 50% of the initial values respectively. Threshold auditory sensation of electrical stimulation significantly decreased by the time of the first connection of the implant compared with the surgical data. Further changes in threshold ESS were relatively small and did not reach statistical significance. | 25,246,204 | [
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Anterolateral thigh myocutaneous flaps as the preferred flaps for reconstruction of oral and maxillofacial defects. | The anterolateral thigh myocutaneous flap is one of the most commonly used flaps in reconstructive procedures, but its application in oral and maxillofacial defects has not been fully determined. Herein, we summarize the application of 1212 anterolateral thigh myocutaneous flaps in the repair of oral and maxillofacial defects and examine their benefits in maxillofacial reconstruction of these defects. Patients were recruited from February 2002 to June 2013 in the Department of Oral and Maxillofacial Surgery of Central South University. All patients underwent reconstructive surgery employing anterolateral thigh myocutaneous flaps. Patient ages ranged from 6 to 82 years with a mean age of 51.2 years. There are 1015 flaps showing single lobe and 197 flaps showing a multi-island pedicle and one of which carries the iliac bone. The largest area among the single flaps was 28 × 12 cm(2), and the smallest was 3 × 2 cm(2). Among the 1212 transferred flaps, 1176 survived and 36 showed necrosis, a survival rate of about 97.0%. The common complications at flap donor site were poor wound healing (10.1%), localized paraesthesia (50.1%), and altered quadriceps force (11.0%). No cases presented with local serious complications, and 90% of patients achieved good functional recovery and aesthetically acceptable results after reconstruction of oral and maxillofacial defects at various locations using anterolateral thigh myocutaneous flaps. The time (23-121 min; average 51 min) for anastomosis of one vein and one artery was significantly less than that for two veins and one artery (45-153 min, average 83 min; p = 0.0003), which indicates one vein anastomosis can significantly reduce the operating time. The anterolateral thigh myocutaneous flaps can be easily obtained and can provide a good amount of muscle for filling dead space and fascia lata. These flaps can be prepared into a separate fat flap, multi-island fascia with iliac bone, and other composite pedicle flaps to meet the various requirements of oral and maxillofacial defects. The subcutaneous fat thickness of the anterolateral area can vary considerably and thus can be used to repair defects requiring different flap thickness. Therefore, the anterolateral thigh myocutaneous free flaps are more suitable for oral and maxillofacial defects than other flaps. | 25,246,225 | [
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Encoding order and developmental dyslexia: a family of skills predicting different orthographic components. | We investigated order encoding in developmental dyslexia using a task that presented nonalphanumeric visual characters either simultaneously or sequentially--to tap spatial and temporal order encoding, respectively--and asked participants to reproduce their order. Dyslexic participants performed poorly in the sequential condition, but normally in the simultaneous condition, except for positions most susceptible to interference. These results are novel in demonstrating a selective difficulty with temporal order encoding in a dyslexic group. We also tested the associations between our order reconstruction tasks and: (a) lexical learning and phonological tasks; and (b) different reading and spelling tasks. Correlations were extensive when the whole group of participants was considered together. When dyslexics and controls were considered separately, different patterns of association emerged between orthographic tasks on the one side and tasks tapping order encoding, phonological processing, and written learning on the other. These results indicate that different skills support different aspects of orthographic processing and are impaired to different degrees in individuals with dyslexia. Therefore, developmental dyslexia is not caused by a single impairment, but by a family of deficits loosely related to difficulties with order. Understanding the contribution of these different deficits will be crucial to deepen our understanding of this disorder. | 25,246,235 | [
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[Clinical characteristics of 192 adult hemophagocytic lymphohistiocytosis]. | To analyze the clinical manifestations, laboratory data, therapy, and prognosis in patients with hemophagocytic lymphohistiocytosis (HLH). A retrospective study was carried out in 192 adult patients with HLH between 2003 and 2013. Of the 192 cases, 70 cases were secondary to cancer and 64 cases secondary to infection. According to HLH-2004 criteria, the coincidence rate of indices were: fever (98.96%), high level of serum ferritin (94.27%), increased level of soluble interleukin- 2 receptor(sCD25) (94.79%), decreased or absent activity of NK cells (94.27%), cytopenias (80.73%), splenomegaly (80.21%), emophagocytosis in bone marrow, spleen or lymph nodes (74.48%), hypofibrinogenemia (50.52%), hypertriglyceridemia (37.50%). In addition, 94.27% of patients were presented with liver dysfunction, 96.35% with infections, and 75.52% with coagulopathy. Incidences of central nervous system symptoms and rash were 19.27% and 20.31%, respectively. Among cancer, infection and rheumatic group, there were statistically differences on white blood cells (WBC), platelet (PLT), sCD25, alanine aminotransferase, aspartate aminotransferase, total bilirubin and globulin(GLO) (P<0.05). The differences of WBC, PLT, albumin (ALB), GLO, brain natriuretic peptide, creatinine, urea nitrogen between survival group and death group had statistical significance. The secondary HLH occurs from various underlined diseases. Cancer, especially T- cell lymphoma, is the main cause, Secondly, it is EB virus infection. The diagnostic sensitive indicators are Persistent fever, higher level of serum ferritin, low or absent NK-cell activity, and increased sCD25 were the most valuable parameters for diagnosis. Cytopenias were not common in early phase of HLH secondary to rheumatic diseases. WBC, PLT, ALB, GLO could be used as the preliminary parameters for diagnosis. Cardiac insufficiency, renal insufficiency and coagulation dysfunction play important roles in prognosis. | 25,246,246 | [
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... |
Reccurent bleeding from Meckel's diverticulum - surgeon's challenge. | The authors of this paper want to share their experience with diagnostic and therapeutic problems in case of chronic small intestinal bleeding from Meckel's diverticulum, which ended with acute episode of massive gastrointestinal bleeding requiring emergent surgery.Despite the progress achieved in diagnosing the sources of gastrointestinal bleeding, the diagnosis of small intestinal bleeding is very frequently beyond the ability of making it right, and thus emergent surgery is often the only possibility of saving the patient's life on the one hand, and allowing stating the correct diagnosis on the other (Fig. 1, Ref. 6). | 25,246,290 | [
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0.1993471,
0.03578776,
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... |
X-linked Recessive Distal Myopathy With Hypertrophic Cardiomyopathy Caused by a Novel Mutation in the FHL1 Gene. | FHL1 gene mutations are associated with reducing body myopathy, X-linked myopathy with postural muscle atrophy, scapuloperoneal myopathy, Emery-Dreifuss muscular dystrophy, and isolated hypertrophic cardiomyopathy. We describe a boy with a family history consistent with X-linked distal myopathy/cardiomyopathy. The boy first presented at age 14 years and was found to have distal wasting and weakness. Echocardiogram revealed hypertrophic cardiomyopathy. Muscle biopsy showed a vacuolar pathology with no reducing bodies. Sequencing of FHL1 revealed a novel hemizygous c.764G>C missense mutation in exon 8. This is the first report of a predominantly distal myopathy with hypertrophic cardiomyopathy occurring secondary to an FHL1 mutation. | 25,246,303 | [
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0.195122,
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... |
Comparison of Effects of Different Dexmedetomidine and Chloral Hydrate Doses Used in Sedation on Electroencephalography in Pediatric Patients. | The aim of this study was to compare the efficacy and safety of different oral chloral hydrate and dexmedetomidine doses used for sedation during electroencephalography (EEG) in children. One hundred sixty children aged 1 to 9 years with American Society of Anesthesiologists physical status I-II who were uncooperative during EEG recording or who were referred to our electrodiagnostic unit for sleep EEG were included to the study. The patients were randomly assigned into 4 groups. In groups D1 and D2, patients received oral dexmedetomidine doses of 2 and 3 µg/kg, respectively. In group C1 and C2, patients received oral chloral hydrate doses of 50 and 100 mg/kg, respectively. The induction time was significantly shorter in group C2 compared with other groups (P = .000). The rate of adverse effects was significantly higher in group C2 compared with the dexmedetomidine groups (D1 and D2; P = .004). In conclusion, dexmedetomidine can be used safely for sedation during EEG in children. | 25,246,305 | [
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0.1440731,
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